Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Recurrence

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Venetoclax

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Patients receive low dose cytarabine SC BID on days 1-10 and milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive low dose cytarabine SC BID on days 1-10, milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17, and venetoclax PO QD on days 1-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Milademetan Tosylate

Courtney DiNardo, MD

This phase I/II trial studies the side effects and best dose of milademetan tosylate and to see how well it works with cytarabine with or without ventoclax in treating participants with acute myeloid leukemia that has come back (recurrent) or that does not respond to treatment (refractory). Milademetan tosylate and ventoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, 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. It is not yet known if giving milademetan tosylate and low-dose cytarabine with or without ventoclax will work better in treating participants with recurrent or refractory acute myeloid leukemia.

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study.

If you are enrolled in Phase 1, the dose of DS-3032b you receive will depend on when you join this study.

If you are enrolled in Phase 2, you will receive DS-3032b at the highest dose that was tolerated in Phase 1.

All participants will receive LDAC at a fixed dose (meaning the dose will not change). If you are assigned to receive it, your dose of venetoclax will not change either. However, if needed because you have side effects, your dose may be adjusted.

Up to 58 participants will be enrolled in this study. All will take part at MD Anderson.

Milademetan Tosylate and Low-Dose Cytarabine With or Without Venetoclax in Treating Participants With Recurrent or Refractory Acute Myeloid Leukemia

A Phase I/II Study of the Oral MDM2 Inhibitor DS-3032b (Milademetan) in Combination With Low Dose Cytarabine (LDAC) in Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML)

As determined by dose limiting toxicity (DLT). MTD is defined the highest dose at which no more than one patient out of 6 patients experience DLTs in the first cycle. A 3+3 algorithm will be applied for dose escalation or dose de-escalation.

Response is Complete Response (CR) + Complete Response with Incomplete Blood Count Recovery (CRi) + Partial Response (PR) + Morphologic Leukemia -Free State (MLFS: CR is Bone marrow blasts \< 5%; absence of circulating blasts and blasts with Auer rods; absence of extra-medullary disease; ANC \>/= 1.0 x 10\^9/L; platelet count \>/= 100 x 10\^9/L. CRi is CR except for ANC \< 1.0 x 10\^9 or platelet count , 100 x 10\^9/L. PR is decreased bone marrow blast % by at least 50% to a value of 5% to 25% and ANC \>/= 1.0 x 10\^9/L; platelet count \>/= 100 x 10\^9/L. MLFS is Bone marrow blasts \< 5%; abcence of blasts with Auer rods; absence of extra-medullary disease; no hematologic recovery required.

Time from date of treatment start until date of death due to any cause or last Follow-up.

Time from date of treatment start until the date of first objective documentation of disease-relapse.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Patients receive low dose cytarabine SC BID on days 1-10 and milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cytarabine: Given SC

Milademetan Tosylate: Given 120 mg PO

Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 0

Patients receive low dose cytarabine SC BID on days 1-10 and milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cytarabine: Given SC

Milademetan Tosylate: Given 200 mg PO

Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 1

Patients receive low dose cytarabine SC BID on days 1-10 and milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cytarabine: Given SC

Milademetan Tosylate: Given 260 mg PO

Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 2

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Courtney DiNardo, MD/ Associate Professor

Patients receive low dose cytarabine SC BID on days 1-10 and milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cytarabine: Given SC

Milademetan Tosylate: Given PO

Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b)

Maximum Tolerated Dose (MTD) (Phase I)

Participants With a Response

Overall Survival

Event Free Survival (EFS)

Patients receive low dose cytarabine SC BID on days 1-10, milademetan tosylate PO QD on days 8-14, 8-21, or 5-7 and 15-17, and venetoclax PO QD on days 1-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cytarabine: Given SC

Milademetan Tosylate: Given PO

Venetoclax: Given PO

Spots Global Cancer Trial Database for milademetan tosylate