Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title: NCI 10147: A Phase II Randomized Study of Topotecan/Carboplatin With or Without Veliparib in Advanced Myeloproliferative Disorders and Chronic Myelomonocytic Leukemia (CMML)

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well topotecan hydrochloride and carboplatin with or without veliparib work in treating patients with myeloproliferative disorders that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced), and acute myeloid leukemia or chronic myelomonocytic leukemia. Drugs used in chemotherapy, such as topotecan hydrochloride and carboplatin, 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. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving topotecan hydrochloride, carboplatin, and veliparib may work better in treating patients with myeloproliferative disorders and acute myeloid leukemia or chronic myelomonocytic leukemia compared to topotecan hydrochloride and carboplatin alone.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To estimate and 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) 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. II. To compare the 2-year disease-free survival (DFS) and overall survival (OS) in response to T/C/V vs. T/C.

III. To detect and compare the presence of minimal residual disease (MRD) remaining after T/C/V vs. T/C.

IV. Evaluate predictive biomarkers of response via assessment of pretreatment impaired homologous recombination via assessment of:

IVa. Next generation sequencing (NGS) panel for genes mutated in myeloid malignancies done as standard of care per institution.

IVb. Functional impairment of deoxyribonucleic acid (DNA) damage response via assessment of pretreatment samples for radiation-induced RAD51 foci.

IVc. 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 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive topotecan hydrochloride IV continuously over 24 hours and carboplatin IV continuously over 24 hours on days 1-5. Treatment repeats every 28-63 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for a minimum of 30 days, or longer. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Atypical Chronic Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Essential Thrombocythemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm
• Myelofibrosis
• Myeloproliferative Disorders
• Polycythemia
• Polycythemia Vera
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Thrombocythemia, Essential
• Thrombocytosis

• NCT number: NCT03289910
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 24, 2018
• Completion date: December 21, 2024