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Study Title Principal Investigator
AN OPEN-LABEL PHASE 1B STUDY OF PF-04449913 (GLASDEGIB) IN COMBINATION WITH AZACITIDINE IN PATIENTS WITH PREVIOUSLY UNTREATED HIGHER-RISK MYELODYSPLASTIC SYNDROME, ACUTE MYELOID LEUKEMIA, OR CHRONIC MYELOMONOCYTIC LEUKEMIA
Recruiting | Leukemia | Multisite
Pfizer Center
A Phase 3, Randomized, Open-Label, Crossover Study of ASTX727 (Cedazuridine and Decitabine Fixed-Dose Combination) Versus IV Decitabine in Subjects With Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) [ASTX727-02]
This Phase 3 study will establish PK equivalence of ASTX727 to IV decitabine in approximately 118 evaluable subjects. Eligible subjects will receive both study treatments: oral investigational drug ASTX727, and IV decitabine, as follows: subjects will be randomly assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other therapy in Cycle 2. In the ASTX727 cycle, subjects will receive the ASTX727 tablet Daily×5. Serial PK measurements (blood draws) will be done on Days 1, 2, and 5, along with pre-dose PK assessments on Days 1-5 and an assessment at 3 hours post dose on Day 3. Subjects will be required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours before and 2 hours after dosing. In the IV decitabine cycle, subjects will receive a 1-hour infusion of IV decitabine 20 mg/m^2 Daily×5. Serial PK measurements will be done on Days 1 and 5, along with pre-dose and 1-hour post-infusion assessments on Day 3. In Cycles ≥3, subjects will receive the ASTX727 tablet Daily×5 in 28-day cycles. (No PK assessments will be done from Cycle 3 onward.)
Open | Leukemia | Multisite
James Lowder
A Phase II Randomized Study of Topotecan/Carboplatin With or Without Veliparib or Placebo in Advanced Myeloproliferative Disorders and CMML
PRIMARY OBJECTIVES: I. To estimate the compare the complete response/complete response with incomplete recovery (CR/CRi) rate of induction therapy with topotecan hydrochloride (topotecan)/carboplatin (T/C) with or without veliparib (V) or placebo (P) in myeloproliferative disorder associated leukemias and chronic myelomonocytic leukemia (CMML). SECONDARY OBJECTIVES: I. To evaluate and compare the toxicities of T/C/V versus (vs.) T/C/placebo. II. To compare the 2-year disease-free survival (DFS) and overall survival (OS) in response to T/C/V vs. T/C/placebo. III. To detect and compare the presence of minimal residual disease (MRD) remaining after T/C/V vs. T/C/placebo. IV. Evaluate predictive biomarkers of response via assessment of pretreatment impaired homologous recombination via assessment of: next generation sequencing (NGS) panel for genes mutated in myeloid malignancies done as standard of care per institution; functional impairment of deoxyribonucleic acid (DNA) damage response via assessment of pretreatment samples radiation-induced RAD51 foci; topotecan-induced stabilization of topoisomerase I-DNA covalent complexes, which has recently been observed to be a critical predictor of response to combination of a topoisomerase I poison and PARP inhibitor in xenografts. V. To evaluate veliparib exposure and contribution to response (efficacy and toxicity). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive veliparib orally (PO) twice daily (BID) on days 1-21 and topotecan hydrochloride intravenously (IV) continuously over 24 hours and carboplatin IV continuously over 24 hours on days 3-7. Treatment repeats every 28-63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive topotecan hydrochloride and carboplatin as in Arm A. Patients also receive placebo PO BID on days 1-21. Treatment repeats every 28-63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Open | Leukemia | Multisite
Keith Pratz
A Phase I Dose Escalation Study With Expansion to Evaluate the Safety of SEPHB4-HSA in Combination With Cytarabine or Liposomal Vincristine in Patients With Relapsed or Refractory Acute Leukemia
PRIMARY OBJECTIVES: I. Characterize the DLTs (dose limiting toxicities) and overall toxicity profile of recombinant EphB4-HSA fusion protein (sEPHB4-HSA) as a single agent and in combination with cytarabine or liposomal vincristine in patients with acute leukemia. SECONDARY OBJECTIVES: I. Estimate the clinical response (including minimal residual disease [MRD]) in blood and bone marrow of sEPHB4-HSA in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia. II. Estimate the clinical response (including MRD) in blood and bone marrow of sEPHB4-HSA in combination with liposomal vincristine in patients with relapsed/refractory acute lymphoid leukemia. III. Estimate the single agent clinical response of sEPHB4-HSA in blood and bone marrow of patients with relapsed/refractory acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). IV. Assess pharmacokinetics of sEPHB4-HSA as a single agent and in combination with cytarabine or liposomal vincristine in patients with leukemia. EXPLORATORY OBJECTIVES: I. Estimate progression-free survival and overall survival in patients treated with sEPHB4-HSA in combination with cytarabine or liposomal vincristine. II. Estimate percentage of patients proceeding to allogeneic stem cell transplantation. III. Correlate expression of EPHB4 leukemic blasts and ephrinB2 in bone marrow microenvironment with response to sEPHB4-HSA. IV. Evaluate the effect of sEPHB4-HSA on downstream protein mediators of the EPHB4 pathway (phosphorylated [p]AKT, pS6) on leukemic blasts and determine if these can be used as biomarkers of response to treatment. V. Profile the immuno-modulatory effects of sEPHB4-HSA on peripheral blood leukocytes and in the tumor microenvironment. OUTLINE: This is a dose-escalation study of recombinant EphB4-HSA fusion protein. Participants are randomized to 1 of 2 arms. ARM A: Participants receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1, 8, 15, and 22 and cytarabine IV over 4 hours on days 1-5. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. ARM B: Participants receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, 15, and 22 and vincristine liposomal IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 3 months.
Suspended | Leukemia | Not Multisite
Akil Merchant
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A Phase1-2 Pharmacokinetic Guided Dose-Escalation and Dose-Confirmation Study of ASTX727, a Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 With Oral Decitabine in Subjects With Myelodysplastic Syndromes (MDS)
Dose levels for the study's second stage will be based on safety and pharmacokinetics.
Not recruiting | Myelodysplastic Syndromes (MDS) | Multisite
Mohammad Azab
A Phase 1/2 Study of Vadastuximab Talirine (SGN-CD33A) in Combination With Azacitidine in Patients With Previously Untreated International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk Myelodysplastic Syndrome (MDS)
In the phase 1 portion of the study, escalating doses of 33A will be evaluated in combination with azacitidine, and a dose of 33A will be selected to proceed to phase 2. The phase 2 portion of the study is randomized, double-blind and placebo-controlled; it is designed to compare the overall response rate (ORR) between 2 study arms.
Not recruiting | Myelodysplastic Syndromes (MDS) | Multisite
Phillip Garfin
A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes.
Suspended | Myelodysplastic Syndromes (MDS) | Multisite
Ignazia Torre
Phase 1B/II Study of Escalating Doses of Pevonedistat (TAK-924, Formerly MLN4924) Administered in Combination With Standard Induction Chemotherapy (Cytarabine and Idarubicin) in Newly Diagnosed High Risk Acute Myelogenous Leukemia (AML)
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed high-risk acute myeloid leukemia. (Phase Ib) II. To determine the composite complete response rate (complete remission [CR] or complete remission with incomplete blood count recovery [CRi]) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed high-risk acute myeloid leukemia. (Phase II) SECONDARY OBJECTIVES: I. To evaluate plasma pharmacokinetic (PK) profiles of pevonedistat when used in combination with cytarabine and idarubicin in the phase Ib part of the study. II. To evaluate the relapse free (RFS), overall survival (OS), safety and tolerability of pevonedistat in combination with cytarabine and idarubicin in the phase II part of the study. TERTIARY OBJECTIVES: I. To evaluate the pharmacodynamics (PD) effects of pevonedistat in combination with cytarabine and idarubicin in acute myelogenous leukemia (AML) blasts. II. To evaluate potential predictive biomarkers of response to pevonedistat in combination with cytarabine and idarubicin in AML. III. To determine the CR without minimal residual disease rate (CR MRD-) of pevonedistat in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia. OUTLINE: This is a phase Ib, dose escalation study of pevonedistat followed by a phase II study. INDUCTION: Patients receive idarubicin intravenously (IV) over 10-15 minutes on days 1-3, cytarabine IV over 1-3 hours on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Patients with gross residual disease on day 14 bone marrow may receive a second course of induction chemotherapy. CONSOLIDATION: Patients who achieve CR and will not undergo bone marrow transplant receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats every 28-35 days for 4 courses in the absence of disease progression or unaccepted toxicity. After completion of study treatment, patients are followed up for at least 30 days, and then every 3 months for 2 years.
Open | Leukemia | Not Multisite
Kevin Kelly
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A Phase II Simon Two-Stage Study of the Addition of Pracinostat to a Hypomethylating Agent (HMA) in Patients With Myelodysplastic Syndrome (MDS) Who Have Failed to Respond or Maintain a Response to the HMA Alone
Not recruiting | Myelodysplastic Syndromes (MDS) | Multisite
Guillermo Garcia-Manero
A Phase 1b/2 Study To Evaluate The Safety And Efficacy Of Pf-04449913, An Oral Hedgehog Inhibitor, In Combination With Intensive Chemotherapy, Low Dose Ara-c Or Decitabine In Patients With Acute Myeloid Leukemia Or High-risk Myelodysplastic Syndrome
Not recruiting | Leukemia | Multisite
Pfizer Center
A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent
This is a Phase III, open-label, randomized, controlled, international study. Approximately 360 patients < 82 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received AZA or DAC for ≤ 9 months and/or ≤ 9 cycles over 12 months and had their last dose of AZA or DAC within 6 months prior to screening will be stratified by: - Very high risk (VHR) vs non-VHR per IPSS-R, and - Geographic region (North America vs Europe vs Asia; because approved products and standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the following 2 treatment groups: - Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2 week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter (N = approximately 240 patients); - Physician's Choice of alternative treatment, which may include any approved or standard-of-care therapy that the patient has not shown to be hypersensitive to, based on frequently used treatment for MDS, as per institutional guidelines, after receipt of HMAs (N = approximately 120 patients). The drugs used in the Physician's Choice arm should be used according to the recommendations, if clinically appropriate, provided in the corresponding Summary of Product Characteristics (SmPC) and Prescribing Information of these drugs. Experimental therapies are not allowed on the PC arm. Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance. For all randomized patients who discontinue study treatment, subsequent therapies with their start and end dates, as well as survival time after treatment discontinuation, will be documented at least monthly until death. Patients in the PC group who progress will not be allowed to cross over to rigosertib. All patients in both treatment groups will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (granulocyte colony-stimulating factor (G-CSF), erythropoietin, and thrombopoietin).
Open | Myelodysplastic Syndromes (MDS) | Multisite
Steven Fruchtman
A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of Deferasirox in Patients With Myelodysplastic Syndromes (Low/Int-1 Risk) and Transfusional Iron Overload
A screening period lasting up to 35 days with two screening visits (Visit 1 and Visit 2 - at least 14 days apart) was used to assess patient eligibility. Eligible patients were randomized in a 2:1 ratio in deferasirox and placebo arms respectively. All patients who were randomized in this study started study treatment at 10 mg/kg/day and could be titrated up to 40 mg/kg/day based on dose modification guidelines. Patients who met a non-fatal event, as specified in the protocol, discontinued from the study treatment and were followed for safety (28 days) and then evaluated with visits every three months if they agreed to move into the post treatment evaluation phase. Subsequent to the evaluation period, or at the end of treatment if a patient and treating physician decided that a patient would not participate in the evaluation period, patients were followed by phone monitoring every six months for their need for iron chelation therapy (ICT) and survival follow-up (OS) until study end. Patients who did not meet a non-fatal event continued study treatment as long as the patient and the treating physician felt it was in the best interest for the patient or until the study terminated. After termination of study treatment, all patients continued to be followed for safety and endpoints during the evaluation period at visits occurring every three months. Subsequent to the evaluation period, or at the end of treatment if a patient and treating physician decided that a patient would not participate in the evaluation period, patients were followed every 6 months for ICTs and OS.
Not recruiting | Myelodysplastic Syndromes (MDS) | Multisite
Novartis Pharmaceuticals
A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
PRIMARY OBJECTIVES: I. To select based on response rate (complete remission, partial remission, or hematologic improvement) either the combination of lenalidomide and azacitidine or the combination of vorinostat and azacitidine for further testing against single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase II) II. To compare overall survival between the combination arm selected in the Phase II portion of the trial to single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase III) SECONDARY OBJECTIVES: I. To estimate relapse-free survival, overall survival and cytogenetic response rate of patients treated on each regimen. II. To estimate the frequency and severity of toxicities of the three regimens in this patient population. III. To investigate in a preliminary manner the frequency of subgroups from prestudy cytogenetic studies and correlate these subgroups with clinical outcomes in this patient population. IV. To collect specimens for banking for use in future research studies. TERTIARY OBJECTIVES: I. To evaluate the prevalence of a pre-specified list of molecular lesions (48 total lesions). II. To assess associations of these lesions with outcomes (response, event-free survival, relapse-free survival, and overall survival). III. To develop a deoxyribonucleic acid (DNA) methylation biomarker predictive of response to DMTi treatment in MDS. IV. To harness gene expression profiles as clinical biomarkers of primary resistance to DMTi in MDS. OUTLINE: Patients are randomized to 1 of 3 treatment arms. In Phase III, patients are randomized to 1 of 2 treatment arms (the combination arm selected in Phase II or the single-agent azacitidine arm). ARM I: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 or days 1-5 and 8-9, and lenalidomide orally (PO) once daily (QD) on days 1-21. ARM II: Patients receive azacitidine as in Arm I. ARM III: Patients receive azacitidine as in Arm I and vorinostat PO twice daily (BID) on days 3-9. In all arms, treatment repeats every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Not recruiting | Leukemia | Multisite
Mikkael Sekeres
A Pilot/Safety Study of sEphB4-HSA in Combination With a Hypomethylating Agent (HMA) for Patients With Relapsed or Refractory Myelodysplastic Syndrome (MDS) and AML Previously Treated With a Hypomethylating Agent
PRIMARY OBJECTIVES: I. To describe the toxicities and assess the tolerability of recombinant EphB4-HSA fusion protein (sEphB4-HSA) in combination with an approved hypomethylating agent (HMA) among patients with myelodysplastic syndrome (MDS) who are refractory to or have lost their response to one or more HMAs and among patients with relapsed/refractory acute myeloid leukemia (AML) previously treated with a HMA. SECONDARY OBJECTIVES: I. To measure the expression of EphB4 among marrow and peripheral blood blasts in patients with MDS & AML at baseline and over the course of treatment. II. To measure the expression of immune check-point activating ligands (such as PD-L1, PD-L2) on marrow and peripheral blood blasts in patients treated with HMA and sEphB4-HSA in combination. III. To profile immune subsets (activated and exhausted T cells, natural killer [NK] cells, T regulatory cells, and myeloid derived suppressor cells) in the peripheral blood and marrow in patients treated with HMA and sEphB4-HSA in combination. IV. To assess efficacy of sEphB4-HSA in combination with an HMA as manifest by International Working Group (IWG) response criteria, as well as time to development of acute myeloid leukemia (AML) in patients with MDS and time to progression. OUTLINE: Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1 and 15. Patients also receive azacitidine IV or subcutaneously (SC) on days 1-7 or days 1-5 and 8-9, or decitabine IV on days 1-5. Administration of recombinant EphB4-HSA fusion protein occurs before or after the HMA (not concurrently). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.
Open | Leukemia | Not Multisite
Casey O'Connell
A Phase I/II Multicenter Study Combining Guadecitabine, a DNA Methyltransferase Inhibitor, With Atezolizumab, an Immune Checkpoint Inhibitor, in Patients With Intermediate or High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
PRIMARY OBJECTIVES: I. To identify a safe dose of guadecitabine in combination with atezolizumab and to assess the safety and tolerability of the combination in patients with myelodysplastic syndrome (MDS) who are refractory to or have lost their confirmed response to one or more hypomethylating agents (HMAs) and in patients with newly diagnosed MDS. II. To evaluate the efficacy of guadecitabine in combination with atezolizumab for the treatment of patients with MDS who are refractory to or have lost their confirmed response to one or more HMAs. III. To evaluate the efficacy of guadecitabine in combination with atezolizumab for the treatment of patients with newly diagnosis MDS. SECONDARY OBJECTIVES: I. To measure the impact of the combination of guadecitabine and atezolizumab on overall survival among patients with relapsed/refractory MDS. II. To measure the impact of the combination of guadecitabine and atezolizumab on overall survival among patients with treatment-naive MDS. III. To evaluate the impact of the combination of guadecitabine and atezolizumab on the duration of response in patients with relapsed/refractory MDS and treatment-naive MDS. IV. To evaluate the impact of the combination of guadecitabine and atezolizumab on transfusion-dependence among patients with relapsed/refractory and treatment-naive MDS. TERTIARY OBJECTIVES: I. To determine the baseline expression/methylation of programmed cell death protein 1 (PD-1) in T cells among patients with relapsed, refractory and treatment-naive MDS. II. To quantify the impact of combination therapy with guadecitabine and atezolizumab on PD-1 expression/methylation in T cells. III. To correlate response with expression/methylation of PD-1 by T cells and with expression of programmed cell death-ligand 1 (PD-L1) in the bone marrow of patients with MDS treated with guadecitabine and atezolizumab. IV. To investigate the expression of tumor antigens on MDS blasts during combination therapy with guadecitabine and atezolizumab V. To investigate the specific T-cell subsets in MDS blood and bone marrow during combination therapy with guadecitabine and atezolizumab. VI. To investigate the specific antigens (epitopes) which are recognized by T-cells in MDS blood and bone marrow during combination therapy with guadecitabine and atezolizumab. OUTLINE: This is a phase I, dose-escalation study of guadecitabine followed by a phase II study. Patients receive guadecitabine subcutaneously (SC) on days 1-5 and atezolizumab intravenously (IV) over 30-60 minutes on days 8 and 22. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 or 90 days and every 6 months thereafter.
Open | Leukemia | Multisite
Casey O'Connell
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