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Slow enrolment
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This study will be divided into two parts, Parts A and B and will enroll patients with relapsed/refractory AML or MDS/chronic myelomonocytic leukemia (CMML) patients who have failed up to 2 prior therapeutic regimens.
Part A is a dose escalation study to explore the safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) profile of DSP107 when administered in combination with azacitidine (AZA).
Part B is a dose escalation study to explore the safety, efficacy, PK and PD profile of DSP107 when administered in combination with AZA and venetoclax (VEN).
Part A is a dose escalation study in up to 4 cohorts of patients designed to test the safety and efficacy of DSP107 administered alone and in combination with AZA. The DSP107 starting dose level in Part A will be 0.3 mg/kg based on aggregate safety, PK and PD data from study DSP107_001, an ongoing study exploring the safety of escalating DSP107 doses in patients with advanced solid tumors. There will be a single DLT evaluation period, lasting 28 days, to determine the safety of DSP107 in combination with AZA. The safety, efficacy and PK data will be used to establish a recommended Phase II dose for potential future expansion cohorts and a starting dose for Part B.
Part B is a dose escalation study in 2 cohorts of patients that will test the safety and efficacy of DSP107 in combination with AZA and VEN. The starting dose for Part B will be at least one dose level lower than the DSP107 dose selected in Part A as being safe and effective in combination with AZA. Once a safe, effective dose has been established in Part B, a recommended phase 2 dose for patients with newly diagnosed AML will be agreed with the FDA at an End-of-Phase 1 meeting.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DSP107 in combination with azacitidine or azacitidine plus venetoclax. | Experimental | DSP107 will be administered by intravenous infusion once weekly during each 28-day cycle to all patients in this study. Azacitidine (75 mg/m2/day) will be administered subcutaneously or intravenously for the first 7 days of every cycle. Patients enrolled in Part B only will also receive venetoclax. During Cycle 1, venetoclax will be dose escalated daily to the goal dose of 400 mg daily. Patients will receive 100 mg on Day 1, 200 mg on Day 2 and 400 mg on Day 3 and onwards. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DSP107 | Biological | DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein. |
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| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (AEs) | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | Duration of the study, estimated to be 12 months |
| Dose Limiting Toxicities (DLT) | A DLT is defined as a clinically significant AE or laboratory abnormality that is related to DSP107 or the combination of DSP107 and AZA, but is unrelated to disease progression, intercurrent illness or concomitant medications | At the end of Treatment Cycle 2 (within 2 months of treatment initiation) |
| Response Rate (RR) including Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) | Response rates will be determined by assessing peripheral blood and bone marrow samples. | Within 6 months of treatment initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | Peripheral and bone marrow samples will be assessed to determine ORR. The ORR will measure the proportion of patients who achieve CR, CRi, complete remission with incomplete hematological recovery (CRh), complete remission with incomplete platelet recovery (CRp) or partial response (PR) within 6 months of treatment initiation, with or without cytogenetic response, hematological improvements and a morphologic leukemia-free state. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Duarte | California | 91010 | United States | ||
| The University of Texas MD Anderson Cancer Center, Department of Leukemia |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C579720 | venetoclax |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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This study will involve sequential enrollment of approximately 36 patients accrued into six dose cohorts, each testing a different DSP107 dose level in combination with azacitidine (Part A) or DSP107 in combination with azacitidine and venetoclax (Part B).
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| Azacitidine | Drug | Azacitidine is an analog of the pyrimidine nucleoside cytidine. |
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| Venetoclax | Drug | Venetoclax is a B-cell lymphoma (BCL)-2 inhibitor |
|
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| Within 6 months of treatment initiation |
| Morphologic Leukemia-Free (MLF) Rate | Peripheral and bone marrow samples will be assessed to determine the proportion of patients who are morphologically leukemia-free within 6 months of treatment initiation. | Within 6 months of treatment initiation |
| Minimal Residual Disease (MRD) Status | Peripheral and bone marrow samples will be assessed to determine minimal residual disease (MRD) status at response and/or the best MRD response during study participation. | Duration of the study, estimated to be 12 months |
| 4-week Mortality Rate | The proportion of patients who die within 4 weeks of treatment initiation. | Within 4 weeks of treatment initiation |
| DSP107 Serum Concentration | Serum samples will be collected to determine circulating levels of DSP107. | Duration of the study, estimated to be 12 months |
| DSP107 anti-drug antibody (ADA) formation | Serum samples will be collected throughout the study for assessment of ADA formation using validated assay. | Duration of the study, estimated to be 12 months |
| Change in Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells | Whole blood samples will be collected throughout the study for immunophenotyping by flow cytometry and/or mass cytometry. | Duration of the study, estimated to be 12 months |
| Houston |
| Texas |
| 77030 |
| United States |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |