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

NCT03289910 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2017-01715ETCTN1014710147UM1CA186691
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Atypical Chronic Myeloid Leukemia; Myelodysplastic/Myeloproliferative Neoplasm; Refractory Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Polycythemia Vera; Acute Myeloid Leukemia; Essential Thrombocythemia; Myelofibrosis; Recurrent Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Response

  Based on published standards for acute leukemias, Complete Response (CR) means less than 5% leukemic blasts in the bone marrow, no blasts in the blood, no longer presence of cytogenetic abnormalities, no longer presence of extramedullary disease, with or without absolute neutrophil count or platelet count recovery; Partial Remission (PR) includes the criteria for Complete Remission except there are 5-25% leukemic blasts in the bone marrow and there is absolute neutrophil count and platelet count recovery; Hematologic Improvement (HI) means the disease has not gotten worse and there is at least a 20% decrease in the leukemic blasts in the bone marrow and/or a decrease in leukemia symptoms. Response = CR, PR, or HI.

  Up to 7 months

Secondary Outcomes (10)

• The Highest Grade Adverse Event Experienced

  Up to 7 months

• Number of Participants Without Disease at Study Completion

  Up to 7 months

• Duration of Disease-free Survival

  Up to 7 months

• Number of Participants Still Alive at Study Completion

  Up to 7 months

• Duration of Overall Survival at the Time of Study Completion

  Up to 7 months

Study Arms (2)

Arm A (veliparib, topotecan hydrochloride, carboplatin)

EXPERIMENTAL

Patients receive veliparib PO BID on days 1-21 and topotecan hydrochloride 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.

Drug: Carboplatin; Drug: Topotecan; Drug: Topotecan Hydrochloride; Drug: Veliparib

Arm B (topotecan hydrochloride, carboplatin)

ACTIVE COMPARATOR

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.

Drug: Carboplatin; Drug: Topotecan; Drug: Topotecan Hydrochloride

Interventions

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)

Arm A (veliparib, topotecan hydrochloride, carboplatin); Arm B (topotecan hydrochloride, carboplatin)

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

Arm A (veliparib, topotecan hydrochloride, carboplatin); Arm B (topotecan hydrochloride, carboplatin)

Veliparib DRUG

Given PO

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

Arm A (veliparib, topotecan hydrochloride, carboplatin)

Topotecan DRUG

Given IV

Also known as: Hycamptamine, Topotecan Lactone

Arm A (veliparib, topotecan hydrochloride, carboplatin); Arm B (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:

• PRE-REGISTRATION ELIGIBILITY CRITERIA
• Newly diagnosed acute myeloid leukemia (AML) associated with antecedent myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia and related undifferentiated myeloproliferative/myelodysplastic disorders)
• Relapsed/refractory AML associated with antecedent myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia and related undifferentiated myeloproliferative/myelodysplastic disorders) who have received two or fewer prior induction chemotherapy courses
• Accelerated phase myeloproliferative disorders per Zeider et al with two or fewer prior therapies
• For aggressive phase myeloproliferative disorders (MPD) (polycythemia vera, essential thrombocythemia, Philadelphia \[Ph\]-negative chronic myelogenous leukemia), one or more of the following criteria must be met: marrow blasts \> 5%, peripheral blood blasts plus progranulocytes \> 10%, new onset or increasing myelofibrosis, new onset or \> 25% increase in hepatomegaly or splenomegaly, new onset constitutional symptoms (fever, weight loss, splenic pain, bone pain). Zeider et al
• For chronic myelomonocytic leukemia (CMML), the following criteria must be met: 5-19% bone marrow blasts (aggressive) or \>= 20% marrow blasts (transformation)
• Bone marrow and/or peripheral blood specimens will be submitted for correlative studies; patients with a dry tap will still be eligible
• RANDOMIZATION ELIGIBILITY CRITERIA
• Bone marrow aspirate and/or peripheral blood specimens were submitted to the central lab and site has confirmation by the local institution that the patient meets one of the criteria specified above
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 or Karnofsky \>= 60%
• Total bilirubin less than 2.0 mg/dL unless due to Gilbert's syndrome, then less than 5.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) less than 5 x institutional upper limit of normal
• Creatinine clearance glomerular filtration rate (GFR) greater than 30 ml/min per modified Cockcroft-Gault formula
• Interval of greater than 4 weeks since allogeneic blood or marrow transplantation (BMT) if performed; and absence of active graft versus host disease (GVHD)
• The effects of veliparib on the developing human fetus are unknown; for this reason and because PARP inhibiting agents as well as topoisomerase inhibitors and platinating agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months following the last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of veliparib administration

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study with the exception of hydroxyurea for cytoreduction; therapy with tyrosine kinase inhibitors (TKIs) directed against JAK2, BCR-ABL or FLT3 will be allowed to be continued until 24 hours prior to start of therapy on trial
• Patients with active uncontrolled infection; antibiotic therapy for fevers, and continuation of treatment of prior infection are allowed
• Patients who have active central nervous system (CNS) disease are excluded; patients with known active CNS leukemia should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patients who are receiving any other investigational agents; patients who have completed therapy with an investigational agent should be off this therapy for at least 5 half-lives or two weeks, whichever is shorter
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib, topotecan or carboplatin
• Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because veliparib is PARP inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with veliparib, breastfeeding should be discontinued if the mother is treated with veliparib; these potential risks may also apply to topotecan and carboplatin used in this study
• Human immunodeficiency virus (HIV)-patients positive patients are not excluded if they have CD4+ cells \>= 250/mm\^3 and negligible viral load and are on a stable combination antiretroviral therapy
• History of uncontrolled seizure disorder, including focal or generalized seizure within the past year

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Richardson DR, Green SD, Foster MC, Zeidner JF. Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options. Curr Hematol Malig Rep. 2021 Feb;16(1):97-111. doi: 10.1007/s11899-021-00608-6. Epub 2021 Feb 20.

  PMID: 33609248 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Thrombocythemia, Essential; Myelodysplastic-Myeloproliferative Diseases; Primary Myelofibrosis; Polycythemia Vera

Interventions

Carboplatin; Topotecan; veliparib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University

JHCCCRO@jhmi.edu

4439273568

Study Officials

• Keith W Pratz

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 21, 2017
• Study Start: September 24, 2018
• Primary Completion: May 31, 2023
• Study Completion (Estimated): December 18, 2026
• Last Updated: April 13, 2026
• Results First Posted: April 2, 2024

Record last verified: 2025-12

Locations

US (6)