Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

NCT00588991 | Completed Phase 1

• 9 other identifiers: NCI-2009-00259CDR0000579626J07837968P30CA006973U01CA062491U01CA069912U01CA070095UM1CA186691
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial is studying the side effects and best dose of veliparib when given together with topotecan hydrochloride with or without carboplatin in treating patients with relapsed or refractory acute leukemia, high-risk myelodysplasia, or aggressive myeloproliferative disorders. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 or by stopping them from dividing. Giving veliparib together with topotecan hydrochloride and carboplatin may kill more cancer cells.

Conditions

Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myeloid Leukemia, Philadelphia Chromosome Negative, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; De Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Myelodysplastic Syndrome; Polycythemia Vera; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of veliparib, determined as the highest dose level where 0/3 or 1/6 experience DLT, measured according to NCI-CTCAE 4.0

  Up to 63 days

• Clinical response (CR, CRi, PR)

  Up to 3 years

Secondary Outcomes (1)

• Pharmacokinetics and pharmacodynamics of veliparib

  Day 1 at pre-treatment, .25, .5, 1, 2, 4, 6, and 8 hours after veliparib and day 4 at pre-veliparib, .25, .5, 1, 2, 4, 6, and 8 hours after the first dose of veliparib

Study Arms (1)

Treatment (veliparib, topotecan hydrochloride, carboplatin)

EXPERIMENTAL

Patients receive veliparib orally twice daily on days 1-8, 1-14, or 1-21 and topotecan hydrochloride with or without carboplatin IV continuously over 120 hours on days 3-7. Treatment repeats every 28-63 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Topotecan Hydrochloride; Drug: Veliparib

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (veliparib, topotecan hydrochloride, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative study

Treatment (veliparib, topotecan hydrochloride, carboplatin)

Topotecan Hydrochloride DRUG

Given IV

Also known as: Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride, Potactasol, SKF S 104864 A, SKF S-104864-A, SKF S104864A, Topotec, Topotecan HCl, topotecan hydrochloride (oral)

Treatment (veliparib, topotecan hydrochloride, carboplatin)

Veliparib DRUG

Given orally

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Treatment (veliparib, topotecan hydrochloride, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of 1 of aggressive MPD or AML out of MPD
• Aggressive phase high-risk myeloproliferative disorders (i.e., polycythemia vera, essential thrombocythemia, or Ph-negative chronic myelogenous leukemia) meeting ≥ 1 of the following criteria:
• Marrow blasts \> 5%
• Peripheral blood blasts plus progranulocytes \> 10%
• New onset or increasing myelofibrosis OR;
• New onset or \> 25% increase in hepatomegaly or splenomegaly
• New onset constitutional symptoms (i.e., fever, weight loss, splenic pain, or bone pain)
• Patients who failed primary induction therapy or relapsed after achieving complete remission are eligible
• No active CNS leukemia; patients with a history of CNS disease must be stable for \> 3 months after treatment and off steroid treatment prior to study enrollment
• Chronic myelomonocytic leukemia meeting either of the following criteria:
• % bone marrow blasts (aggressive)
• At least 20% marrow blasts (transformation)
• ECOG performance status 0-2
• No hyperleukocytosis with \>= 50,000 blasts/uL
• AST, ALT, and alkaline phosphatase =\< 5 times upper limit of normal

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Thrombocythemia, Essential; Hematologic Neoplasms; Myelodysplastic Syndromes; Polycythemia Vera; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Carboplatin; Topotecan; veliparib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Neoplasms by Site; Bone Marrow Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Keith W Pratz

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: January 9, 2008
• Study Start: February 4, 2008
• Primary Completion: November 1, 2016
• Study Completion: November 16, 2016
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

US (2)