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Study Title Principal Investigator
SWOG-S0910: A Phase II Study of Epratuzumab (NSC-716711) in Combination with Cytarabine and Clofarabine for Patients with Relapsed or Refractory Ph-Negative Precursor B-cell Acute Lymphoblastic Leukemia (ALL)
OBJECTIVES: - To test whether the complete remission (CR) rate (CR and incomplete CR) in adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia is sufficiently high after treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation. - To estimate the frequency and severity of toxicities associated with the dosing schedule of cytarabine, clofarabine, and epratuzumab used in this study. - To investigate, preliminarily, the effect of laboratory correlates (minimal post-treatment residual disease) and cytogenetic factors on prognosis in this patient population. (Not reported here due to limited MRD data) OUTLINE: This is a multicenter study. Patients receive cytarabine IV over 2 hours on days 1-5, clofarabine IV over 1 hour on days 2-6, and epratuzumab IV over at least 1 hour on days 7, 14, 21, and 28 in the absence of disease progression or unacceptable toxicity*. NOTE: * Prophylactic intrathecal methotrexate is required for patients < 22 years of age, and is recommended (but not required) for patients ≥ 22 years of age. Blood samples, bone marrow samples, and/or tumor tissue samples may be collected for further laboratory analysis. Patients are followed up every 3 months for 2 years, then annually for 3 years (until 5 years after registration).
Active, not recruiting | Leukemia | Multisite
Vinod Pullarkat
Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma
This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with relapsed or refractory lymphoma or multiple myeloma. The following dosing schedules may be examined, all consisting of 21-day cycles and including: (i) continuous once daily (QD), (ii) twice weekly on Days 1, 4, 8, 11, 15, 18 (BIW) (iii) thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 (TIW) (iv) four days on/three days off on Days 1-4, 8-11, and 15-18 (4/3), and (v) five days on/two days off on Days 1-5, 8-12, and 15-19 (5/2) Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of DLT, each subject will be treated for a minimum of 21 days, and may continue to receive additional treatment until disease progression has been documented or other treatment discontinuation criteria have been met. MTD or BED expansion cohorts of up to 36 evaluable (e.g., up to 12 subjects in each of 2 or 3 specific tumor types or subtype) to better define the safety, tolerability and preliminary antitumor and pharmacodynamic activity of the study treatment, as well as suitability as an RP2D and schedule. Safety and tolerability will be assessed by the incidence and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee (SRC) comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment. The antitumor activity of study treatment will be assessed according to standard response criteria as appropriate for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma). Exploratory biological markers of activity will be assessed in peripheral blood mononuclear cells (PBMC), plasma and tissue specimens (skin, tumor and bone marrow samples, where available).
Completed | Lymphoma | Multisite
Kevin Kelly
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An Open-label, Randomized Phase 3 Study Of Inotuzumab Ozogamicin Compared To A Defined Investigator's Choice In Adult Patients With Relapsed Or Refractory Cd22-positive Acute Lymphoblastic Leukemia (All)
Recruiting | Leukemia | Multisite
0C-11-1 Ph1-66 Phase I Pharmacokinetic Study of Belinostat for Solid Tumors and Lymphomas in Patients with Varying Degrees of Hepatic Dysfunction
Belinostat looks promising for the treatment of patients with cancer, having activity in several tumor types as a single therapy and in combination. Exploring appropriate dosing for patients with varying degrees of abnormal liver function would benefit patients with many diseases. Belinostat is broken down in the liver and is also excreted primarily through the liver. Therefore, belinostat dosing in patients with abnormal liver function will be explored in this phase I clinical trial to establish dosing guidelines. The primary objectives of this study in patients with varying degrees of liver function are to establish safety and tolerability of belinostat given on days 15 of 21-day cycles, define the maximum tolerated dose (MTD) and recommended dose of belinostat given on days 15 of 21-day cycles, and to evaluate the drug levels (pharmacokinetics (PK)) of one dose of belinostat (400 mg/m2).Patients will be divided into four groups according to their liver function: normal liver function (Cohort 1), mild abnormal liver function (Cohort 2), moderate abnormal liver function (Cohort 3), and severe abnormal liver function (Cohort 4). Patients will have screening tests/procedures done to see if they are eligible for the study. Once they are deemed eligible, they will be assigned to one of the cohorts. Participants will be given belinostat through a vein in their arm for 30 minutes. They will take the study drug on Days 1-5 during each 21 day cycle, except for cycle 1. On Day -7, cycle 1, participants will receive an extra dose of belinostat and have PK blood draws done at the Clinical Trials Unit. During each cycle, they will have a physical exam, vital signs, assessment of performance status, blood draws, assessment of their tumor with radiographic scans, monitoring for compliance to treatment and monitoring for side effects. Patients will continue the treatment until their disease worsens, they cannot tolerate the side effects, they are physically unable to continue, at the decision of the study doctor, or they decide to withdraw from the study. Participants will be followed for 30 days after the last dose is given or until one of the following occurs: they enroll on another study (phase 0 or early phase I), they receive standard of care, or death, whichever comes first. The follow-up will consist of a phone call between Days 27-30 after the last dose to evaluate side effects that were ongoing and any new events that might be related to the therapy. Unacceptable side effects related to the study drug that have not resolved by Day 30 post-treatment will be followed through twice weekly phone calls until they stabilize or resolve. Participants will be removed from study for one of the following reasons: completed 30-day followup period, side effects are unresolved but stabilized, they enroll on another study (phase 0 or early phase I), or receive standard of care. The study uses a 3+3 design. A minimum of 2 and a maximum of 6 participants will be accrued in each abnormal liver function Cohort (2-4) at each dose level, and 12 patients will be entered at the recommended dose level in Cohort 1. MTD will not be established for the normal cohort as that is already known. Three additional patients will be accrued to the MTD levels (following establishment of MTD for that cohort in the first 6 patients at that dose level) for each abnormal liver function cohort to allow additional information to be gained at these levels. Some patients may need to be replaced if they are not evaluable based on protocol guidelines. As long as < 33% of the patients treated at a given dose level experience a dose limiting side effect, that dose level will be considered the MTD.
Recruiting | Lymphoma | Multisite
Heinz-Josef Lenz
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SWOG-1318 A Phase II Study of Blinatumomab (NSC-765986) and POMP (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia-Chromosome Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) and of Dasatinib (NSC-732517), Prednisone and Blinatumomab for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia-Chromosome Positive (Ph+) ALL
PRIMARY OBJECTIVES: I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP (prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance. II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid based induction followed by blinatumomab treatment in combination with dasatinib followed by dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL, relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory). SECONDARY OBJECTIVES: I. To evaluate toxicities in these patient populations treated with these regimens. II. To estimate the rates of complete response (CR), complete remission with incomplete count recovery (CRi) and disease-free survival in Ph-negative patients. III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL. IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the time to achieve MRD negativity (exploratory analysis). V. To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study. OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia chromosome status. COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS): INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 18 courses in the absence of disease progression or unacceptable toxicity. COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS): INDUCTION: Patients receive dasatinib PO twice daily (BID) on days 1-84 and prednisone PO on days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and dasatinib PO once daily (QD) on days 1-42. Treatment repeats every 42 days for 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive dasatinib PO BID on days 1-28 and prednisone PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually until 10 years from initial registration.
Recruiting | Leukemia | Multisite
Akil Merchant
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13NHL-12-1: PHI-69 A Phase I Study of Ipilimumab in Combination with Rituximab in Patients with Relapsed/Refractory CD20+ B-Cell Lymphoma
PRIMARY OBJECTIVES: I. To determine a recommended phase II dose for ipilimumab in combination with rituximab. SECONDARY OBJECTIVES: I. To obtain preliminary information on the effect of adding ipilimumab to rituximab in regard to: immune response; clinical anti-tumor response/overall remission rate (ORR) (complete remission + partial remission); progression free survival (PFS). OUTLINE: This is a dose-escalation study of ipilimumab followed by a randomized study. PART I: INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes once every 3 weeks for 12 weeks and rituximab IV over 2-6 hours once weekly for 4 weeks. MAINTENANCE: Patients receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year. PART II: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.
Active, not recruiting | Lymphoma | Multisite
Sikander Ailawadhi
A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
Active, not recruiting | Lymphoma | Multisite
Medical Monitor
9L-11-7: A Phase 2 Study of SAR245409 in Patients with Relapsed or Refractory Mantle Cell Lymphoma, Follicular Lymphoma, or Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
There is a 21 day screening period followed by 28 day cycles. Patients will continue to receive SAR245409 as long as there is clinical benefit or until a study withdrawal criterion is met. The last posttreatment visit will be 30 days after the last dose or until IMP-related toxicities have resolved or are deemed irreversible, whichever is later.
Completed | Lymphoma | Multisite
Ann Mohrbacher
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SWOG-S0806: A Phase I/II Trial of Vorinostat (SAHA) (NSC-701852) in Combination with Rituximab-CHOP in Patients with Newly Diagnosed Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL)
PRIMARY OBJECTIVES: I. To find a safe dose of vorinostat to be used in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) (vorinostat-R-CHOP). (Phase I) II. To estimate the 2-year progression-free survival (PFS) rate in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with vorinostat and R-CHOP therapy (vorinostat-R-CHOP). (Phase II) III. To estimate the response rate (complete and partial) and 2-year overall survival rate. (Phase II) IV. To evaluate the toxicity of vorinostat-R-CHOP in patients with newly diagnosed DLBCL. (Phase II) V. To assess whether pre-treatment acetylation status of histones, expression of major histocompatibility complex (MHC) class II genes, and/or percentage of cluster of differentiation (CD)8+ tumor infiltrating lymphocytes correlate with progression-free survival. (Phase II) VI. To explore whether treatment with vorinostat-R-CHOP increases histone acetylation, alters expression of MHC class II proteins, or alters percentage of T-cell subsets (CD8+, CD4+, forkhead box P3 [FOXP3]+) or infiltrating macrophages. (Phase II) VII. To explore whether histone acetylation status of tumor tissues correlates with MHC class II expression of peripheral blood B cells and lymphocyte subsets. (Phase II) VIII. To explore whether the change in systemic levels of immune cytokines with vorinostat-R-CHOP correlates with lymphoma symptoms, response, progression-free or overall survival. (Phase II) OUTLINE: This is a phase I, dose escalation study of vorinostat followed by a phase II study. Patients receive vorinostat orally (PO) once daily on days 1-5 or 1-9 (according to dose level), rituximab intravenously (IV), cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for 2 years, and then annually for 3 years.
Active, not recruiting | Lymphoma | Multisite
Anil Tulpule
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Phase 3 Study of Study to Evaluate Marqibo® in the Combination Chemotherapy in the Treatment of Subjects >or=60 Years Old With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)
A phase 3, multicenter, randomized study to evaluate the substitution of Marqibo® (Vincristine Sulfate Liposomes Injection, VSLI) for standard Vincristine Sulfate Injection (VSI) in the induction, intensification, and maintenance phases of combination chemotherapy in the treatment of subjects >or= 60 years old with newly diagnosed acute lymphoblastic leukemia (ALL).
Terminated | Leukemia | Multisite
Susan O'Brien
CTSU-9177: Phase II Study of Dose-Adjusted EPOCH+/- Rituximab in Adults with Untreated Burkitt Lymphoma, C-Myc Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma
Background: - Burkitt lymphoma/leukemia (BL) is highly curable. Standard treatment employs doseintense multi-agent chemotherapy and though effective is associated with high morbidity. Therefore, novel approaches are needed that improve the therapeutic index of BL while maintaining or improving efficacy. In HIV+ BL, outcome has been poor, mainly due to the use of CHOP based regimens in this disease. - Two NCI phase II trials have used EPOCH chemotherapy with 1 or 2 doses of rituximab (R) per cycle in untreated BL. (Dose-adjusted) DA-EPOCH-Rituximab has been used in16 HIV negative BL, and 8 HIV positive patients have received 3 to 4 cycles of EPOCHRR to minimize toxicity and risk of opportunistic infections. All patients remain in continuous remission. Treatment was very well tolerated and represents a novel therapeutic strategy in BL. - This trial seeks to assess the effectiveness of a risk adaptive approach with DA-EPOCHR in untreated BL (HIV+/-). Because this treatment represents a major conceptual departure from standard treatment, it is important to obtain additional Phase II results in limited/advanced stage BL -c-MYC positive DLBCL is a rare variant of DLBCL. There is very little data on the biology of this disease and what the optimal therapeutic approach should be has not been defined. Therefore, based on our impression that this behaves aggressively and is likely characterized by a high tumor proliferation rate, we plan to accrue patients with this disease in addition to BL patients. -Plasmablastic lymphoma, another variant of DLBCL is frequently characterized by the activation of MYC and has had a poor outcome historically with standard treatment. We plan to include these patients in the study also. As they are CD20 negative, they will receive DA-EPOCH without Rituximab. Objectives: - Determine PFS, EFS and OS of risk adaptive DA-EPOCH-R in untreated BL and c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma. - Assess predictive value of early FDG-PET/CT scans on PFS. - Obtain pilot comparative molecular profiling in HIV negative and positive BL and c- MYC + DLBCL, including c-MYC+ plasmablastic lymphoma. Eligibility: -Burkitt lymphoma, c-MYC + DLBCL and c-MYC + plasmablastic lymphoma age (Bullet) 18 years. -No prior treatment except limited-field radiotherapy, short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis. -Adequate major organ function unless impairment due to lymphoma. Study Design: -Phase II Study of risk adapted DA-EPOCH-R in BL, c-MYC + DLBCL and DA-EPOCH in c-MYC+ plasmablastic lymphoma - Low risk: DA-EPOCH-RR x 3 cycles. - High risk , c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma : DA-EPOCH (+/-) R x 6 cycles or 8 cycles in select patients. - CSF cytology and flow cytometry for analysis of BL. - High Risk CSF negative - Prophylactic intrathecal treatment - CSF positive - Active intrathecal treatment - FDG-PET/CT pre- and post-cycle 2 in all patients. - A total of 194 patients will be enrolled in the protocol.
Suspended | Lymphoma | Multisite
Anil Tulpule
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0S-11-12: PhI-67 Phase I Study of the Aurora Kinase A Inhibitor MLN8237 in Combination with the Histone Deacetylase Inhibitor Vorinostat in Lymphoid Malignancies
PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD) of MLN8237 (alisertib) when given in combination with vorinostat and to select a dose and schedule for further testing (recommended Phase 2 dose: RP2D) in patients with lymphoid malignancies. II. To describe the toxicities of MLN8237 when given in combination with vorinostat on a 21-day schedule. III. To determine any clinical responses with MLN8237 in combination with vorinostat. IV. To compare the plasma pharmacokinetics of MLN8237 when given alone and in combination with vorinostat. V. To perform immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis to determine aurora kinase A (AURKA) expression in archival formalin-fixed paraffin-embedded sections from the most recent available tumor specimens of patients. VI. To perform correlative studies for apoptosis and proliferation on bone marrow and lymph node specimens, where available, obtained from patients in the expanded cohort at RP2D. OUTLINE: This is a dose-escalation study of alisertib. Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 or days 1-3 and 8-10, and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.
Active, not recruiting | Lymphoma | Multisite
Sikander Ailawadhi
13NHL-14-3: Phase 3 Randomized, Double-Blind, Placebo Controlled, Multicenter Study to Compare the Efficacy and Safety of lenalidomide (CC-5013) plus R-Chop Chemotherapy (R2-Chop) versus Placebo plus R-Chop Chemotherapy in Subjects with Previously Untreated Activated B-Cell Type Diffuse Large B-Cell Lymphoma
This randomized, placebo controlled study is designed to evaluate the efficacy and safety of R2-CHOP chemotherapy versus placebo-R-CHOP chemotherapy in previously untreated ABC typeDiffuse Large B-Cell Lymphoma (DLBCL). The study is divided into the Screening Period, Treatment Period, and Follow-up Period. There is biological possibility and also preclinical data that provide strong support for whylenalidomide should be expected to enhance the efficacy of the current standard of care R-CHOP in the treatment of the ABC type of DLBCL. Lenalidomide suppresses the proliferation of ABCcells in DLBCLand delays tumor growth in a human mouse model. In addition, studies also show enhancement of antibody dependent cell toxicity to cancer cells. Primary objective is to evaluate the efficacy and safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in subjects who have previously untreated ABC type Diffuse Large B-Cell Lymphoma.Participants will receive protocol specified treatments for 6 cycles. Study treatments in a 21-day cycle are: lenalidomide / placebo Days 1 14; rituximab, cyclophosphamide, doxorubicin, and vincristine Day 1; prednisone Days 1 5Primary Endpoint is Progression-free Survival.
Recruiting | Lymphoma | Multisite
Anil Tulpule
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0S-11-4 PhII-118 ABT-888 Phase II Randomized Trial of the Combination of ABT-888 With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal or Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, Triple-Negative Breast Cancer, and Low-Grade Non-Hodgkins Lymphoma
Background: - The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of DNA repair mechanisms. - Individuals with deleterious mutations in the BRCA1 or BRCA2 tumor suppressor genes have an increased risk of developing breast and ovarian cancers due to impaired or defective DNA damage repair; these individuals have an increased susceptibility to DNA-damaging agents and PARP inhibitors. Inhibition of PARP inhibits the repair of DNA damage caused by alkylating agents such as cyclophosphamide. - Metronomic cyclophosphamide has demonstrated efficacy in several tumor types. The PARP inhibitor ABT-888 has been shown to potentiate the action of cyclophosphamide in xenograft models. This combination is well tolerated in a Phase I study and showing promising activity. Objectives: - Compare the response rate (complete response (CR) + partial response (PR)) of the combination of ABT-888 with metronomic oral cyclophosphamide to the response rate (CR+PR) of metronomic oral cyclophosphamide in patients with deleterious BRCA mutations and refractory ovarian cancer or patients with primary peritoneal or ovarian high-grade serous carcinoma or fallopian tube cancer. - Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral cyclophosphamide to the response rate (CR+PR) of single-agent oral cyclophosphamide in patients with triple-negative metastatic breast cancer, stratified for deleterious BRCA mutation. - Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral cyclophosphamide to the response rate (CR+PR) of single-agent metronomic oral cyclophosphamide in patients with refractory low-grade lymphomas. Secondary Objectives: - Determine PAR levels in tumor biopsies, evaluate in archival tissue whether patients tumors have mutations in genes involved in DNA damage repair (e.g., BRCA/Fanconi anemia/protein 53 (p53)), perform exploratory gene expression profiling to correlate PARP messenger ribonucleic acid (mRNA) levels or BRCA mutation status with response to therapy, count circulating tumor cells (CTCs), and determine H2AX levels in CTCs and tumor biopsies (National Cancer Institute (NCI) clinical center only). Eligibility: -Adults with refractory BRCA-positive ovarian cancer, primary peritoneal or ovarian high-grade serous carcinoma, fallopian tube cancer, triple-negative breast cancer, or low-grade lymphoid malignancies (non-Hodgkin's lymphoma) whose disease has progressed following at least one line of therapy. Study Design: - This is a randomized, multi-histology Phase II trial with patients enrolled into 3 cohorts: BRCA-positive ovarian cancer or primary peritoneal or ovarian high-grade serous carcinoma or fallopian tube cancer (A); triple-negative breast cancer (B); or low grade non-Hodgkin's lymphoma (C). Patients in cohort A will be randomized to the combination of ABT-888 with metronomic oral cyclophosphamide or metronomic oral cyclophosphamide alone. Patients in cohort B will be randomized to the combination of ABT-888 with metronomic oral cyclophosphamide or metronomic oral cyclophosphamide alone. Patients in cohort C will be randomized to the combination of ABT-888 with metronomic oral cyclophosphamide or metronomic oral cyclophosphamide alone. - Cyclophosphamide (50 mg) and ABT-888 (60 mg) will be administered orally once a day, continuously in 21-day cycles.
Terminated | Breast Cancer | Multisite
Agustin Garcia
CTSU-E1411: Intergroup Randomized Phase II Four Arm Study In Patients >- 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB ’ R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV’ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB ’ LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV ’ LR)
OBJECTIVES: Primary - To determine whether the addition of bortezomib (RBV) to an induction regimen of rituximab-bendamustine hydrochloride (RB) improves progression-free survival (PFS) compared to RB alone in patients ≥ 60 years of age with previously untreated mantle cell lymphoma. - To determine whether the addition of lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV improves PFS compared to consolidation rituximab alone in this patient population. Secondary - To determine whether the addition of bortezomib to induction therapy improves the positron emission tomography (PET)-documented complete response (CR) rate compared to RB alone. - To determine the objective response rate (ORR) for RB and RBV. - Among patients who do not have PET-documented CR at the end of induction, to determine whether the addition of lenalidomide to consolidation therapy improves CR and ORR compared with rituximab alone. - To determine overall survival (OS) in the treatment arms. - To determine safety, with attention to the addition of bortezomib in the induction regimen and lenalidomide-rituximab (LR) as consolidation therapy. - To collect paraffin-embedded tissue for creation of tissue microarray. - To collect and bank serum and blood mononuclear cells for future studies. - To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11 expression by immunohistochemistry; and Micro-RNA levels by microarray). - Using patient-reported outcomes data, to determine the extent and severity of neuropathy associated with the addition of bortezomib to induction treatment. - Using patient-reported outcomes data, to determine the extent and severity of fatigue associated with the addition of lenalidomide to consolidation treatment. - To evaluate the effects of the addition of bortezomib and lenalidomide on patient-reported health-related quality of life. - To evaluate the effects of bortezomib-related neuropathy on patient-reported health-related quality of life. - To evaluate the response of lymphoma-specific symptoms to treatment. - Using longitudinal patient-reported outcomes data, to describe the trajectory of lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life prior to, during, and following treatment among older adults with MCL. Tertiary - To assess the proportion of patients up and down staging when fludeoxyglucose F 18- (FDG) PET/CT is added to standard Ann Arbor staging. - To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and PFS. - Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the correlation of interim FDG-PET/CT imaging with response rate and PFS both during induction and consolidation therapy. - To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total tumor burden, and association with pathology features (blastoid variant vs other, and Ki67) in the setting of MCL. - To assess differences in overall and CR rates when using Deauville vs International Harmonization Project FDG-PET/CT interpretation criteria. - To determine whether there is a correlation between FDG-PET/CT response and residual disease assessment by molecular and/or flow cytometric techniques. - To determine whether the number of malignant cells in circulation predict the number of cells in marrow. - To determine whether the number of malignant cells in circulation/in marrow at the end of induction correlate with CR and 2-year PFS. - To determine whether there is a higher rate of minimal residual disease (MRD) negativity among patients randomized to RBV as compared with RB, and among patients treated with LR maintenance compared with rituximab. - To compare the two methods of MRD detection - molecular techniques and flow cytometry - as prognostic markers for outcome. OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients are randomized to 1 of 4 treatment arms. - Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. - Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. - Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. - Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. - Arm C: Patients receive induction therapy comprising rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. - Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. - Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. - Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo blood and bone marrow sample collection at baseline and during treatment for correlative studies. Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires at baseline and periodically during study and follow up. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 10 years.
Recruiting | Lymphoma | Multisite
Anil Tulpule
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