NCT04752163

DS-1594b With or Without Azacitidine, Venetoclax, or Mini-HCVD for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

An Open-Label Phase 1/2 Multi-Arm Study of DS-1594b as a Single-Agent and in Combination With Azacitidine and Venetoclax or Mini-HCVD for the Treatment of Patients With Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the effect of DS-1594b with or without azacitidine, venetoclax, or mini-HCVD in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has come back (recurrent) or not responded to treatment (refractory). Chemotherapy drugs, such as azacitidine, venetoclax, and mini-HCVD, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. DS-1594b may inhibit specific protein bindings that cause blood cancer. Giving DS-1594b, azacitidine, and venetoclax, or mini-HCVD may work better in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia.

Detailed description

OUTLINE: This is a phase I, dose-escalation study of DS-1594b followed by a phase II study. PHASE I: Patients receive DS-1594b orally (PO) twice daily (BID) on days 1-28 in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are assigned to 1 of 4 cohorts. COHORT A: Patients with MLLr receive DS-1594b PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT B: Patients with NPM1m receive DS-1594b PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT C: Patients receive DS-1594b PO BID on days 1-28, venetoclax PO QD on days 1-28, and azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT D: Patients receive DS-1594b PO BID on days 1-28. For cycles 1, 3, 5, 7, patients also receive cyclophosphamide IV over 3 hours on days 1-3, mesna IV over 24 hours on days 1-3, vincristine IV on days 1 and 11, dexamethasone PO or IV on days 1-4 and 11-14, filgrastim SC on days 1-28, methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, and cytarabine IT on day 7 of cycles 1 and 3. For cycles 2, 4, 6, 8, patients also receive methotrexate IV over 24 hours on day 1, cytarabine BID IV over 3 hours on days 2 and 3, leucovorin IV or PO every 6 hours (Q6H) starting 12 hours after completion of methotrexate, filgrastim SC days 1-28, cytarabine IT on day 5-8 of cycles 2 and 4 and methotrexate IT on days 8-11 of cycles 2 and 4. Patients with CD20 expression may also receive rituximab IV on days 1 and 11 of cycles 1 and 3 and days 1 and 8 of cycles 2 and 4. Cycles repeat every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients may then receive DS-1594b PO BID on days 1-28, vincristine IV over 15 minutes on day 7 and prednisone PO BID on days 1-5. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at days 30 and 100.

Conditions

• Hematopoietic and Lymphoid Cell Neoplasm
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Chronic Myelomonocytic Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Chronic Myelomonocytic Leukemia
• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	DS-1594b	Given DS-1594b PO
DRUG	Azacitidine	Given IV or SC
DRUG	Cyclophosphamide	Given IV
DRUG	Cytarabine	Given IT
DRUG	Dexamethasone	Given PO or IV
BIOLOGICAL	Filgrastim	Given SC
DRUG	Leucovorin	Given IV or PO
DRUG	Mesna	Given IV
DRUG	Methotrexate	Given IT
DRUG	Prednisone	Given PO
BIOLOGICAL	Rituximab	Given IV
DRUG	Venetoclax	Given PO
DRUG	Vincristine	Given IV

Timeline

• Start date: 2021-03-25
• Primary completion: 2023-11-08
• Completion: 2023-11-08
• First posted: 2021-02-12
• Last updated: 2025-05-23
• Results posted: 2025-05-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study