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NCT03289910 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-06-23

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With a Response

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outcome · POSTED

The Highest Grade Adverse Event Experienced

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outcome · POSTED

Number of Participants Without Disease at Study Completion

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outcome · POSTED

Duration of Disease-free Survival

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outcome · POSTED

Number of Participants Still Alive at Study Completion

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outcome · POSTED

Duration of Overall Survival at the Time of Study Completion

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outcome · POSTED

Number of Participants With Minimal Residual Disease (MRD) After Treatment

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outcome · POSTED

Distribution of Mutations in Deoxyribonucleic Acid (DNA) Repair Defects Via Assessment in Leukemia Mutation Panel

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outcome · POSTED

Frequency of Patients With Functional Impairment of DNA Damage Response Via Assessment With RAD51 Assay

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outcome · POSTED

Topotecan-induced Stabilization of Topoisomerase I-DNA Covalent Complexes

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outcome · NOT POSTED

Pharmacokinetic Sampling Studies Measured Using a Validated Liquid Chromatography/Tandem Mass Spectrometric Method in Plasma and Bone Marrow

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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 * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: Carboplatin
    2. Drug: Topotecan
    3. Drug: Topotecan Hydrochloride
    4. Drug: Veliparib
    label
    Arm A (veliparib, topotecan hydrochloride, carboplatin)
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Drug: Carboplatin
    2. Drug: Topotecan
    3. Drug: Topotecan Hydrochloride
    label
    Arm B (topotecan hydrochloride, carboplatin)
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Arm A (veliparib, topotecan hydrochloride, carboplatin)
    2. Arm B (topotecan hydrochloride, carboplatin)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  2. arm Group Labels
    1. Arm A (veliparib, topotecan hydrochloride, carboplatin)
    2. Arm B (topotecan hydrochloride, carboplatin)
    description
    Given IV
    name
    Topotecan
    other Names
    1. Hycamptamine
    2. Topotecan Lactone
    type
    DRUG
  3. arm Group Labels
    1. Arm A (veliparib, topotecan hydrochloride, carboplatin)
    2. Arm B (topotecan hydrochloride, carboplatin)
    description
    Given IV
    name
    Topotecan Hydrochloride
    other Names
    1. Evotopin
    2. Hycamptamine
    3. Hycamtin
    4. Nogitecan Hydrochloride
    5. Potactasol
    6. SKF S 104864 A
    7. SKF S-104864-A
    8. SKF S104864A
    9. Topotec
    10. Topotecan HCl
    11. topotecan hydrochloride (oral)
    type
    DRUG
  4. arm Group Labels
    1. Arm A (veliparib, topotecan hydrochloride, carboplatin)
    description
    Given PO
    name
    Veliparib
    other Names
    1. ABT 888
    2. ABT-888
    3. ABT888
    4. PARP-1 inhibitor ABT-888
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
SINGLE
who Masked
  1. PARTICIPANT
primary Purpose
TREATMENT
Enrollment
count
25
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Number of Participants With a Response
    time Frame
    Up to 7 months
secondary Outcomes
  1. description
    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
    measure
    The Highest Grade Adverse Event Experienced
    time Frame
    Up to 7 months
  2. description
    Study completion was either death or completion of all protocol-specified activities, whichever came first. Participants who came off study due to disease-related death were counted as having disease.
    measure
    Number of Participants Without Disease at Study Completion
    time Frame
    Up to 7 months
  3. description
    Disease-free survival is defined as participants who are still alive and without disease at study completion. Study completion was either death or completion of all protocol-specified activities, whichever came first.
    measure
    Duration of Disease-free Survival
    time Frame
    Up to 7 months
  4. description
    Study completion was either death or completion of all protocol-specified activities, whichever came first.
    measure
    Number of Participants Still Alive at Study Completion
    time Frame
    Up to 7 months
  5. description
    Study completion was either death or completion of all protocol-specified activities, whichever came first. Duration was measured from the date of registration to the participant's study completion date.
    measure
    Duration of Overall Survival at the Time of Study Completion
    time Frame
    Up to 7 months
  6. description
    Minimal residual disease (MRD) refers to a small number of leukemic cells that remain after treatment.
    measure
    Number of Participants With Minimal Residual Disease (MRD) After Treatment
    time Frame
    Up to 7 months
  7. description
    Will be summarized using descriptive statistics. The association response will be described with appropriate tests for continuously measured biomarkers (t tests, Wilcoxon rank sum tests) and categorical biomarkers (Fisher's exact test). Descriptive analyses will be performed for the whole cohort and also separately for Arms A and B. Differential treatment outcomes for patient subgroups may be explored using appropriate tests for interactions.
    measure
    Distribution of Mutations in Deoxyribonucleic Acid (DNA) Repair Defects Via Assessment in Leukemia Mutation Panel
    time Frame
    Baseline
  8. description
    Will be reported with exact binomial 95% confidence intervals. The association response will be described with appropriate tests for continuously measured biomarkers (t tests, Wilcoxon rank sum tests) and categorical biomarkers (Fisher's exact test). Descriptive analyses will be performed for the whole cohort and also separately for Arms A and B. Differential treatment outcomes for patient subgroups may be explored using appropriate tests for interactions.
    measure
    Frequency of Patients With Functional Impairment of DNA Damage Response Via Assessment With RAD51 Assay
    time Frame
    Baseline
  9. description
    Topotecan-induced stabilization of topoisomerase I-DNA covalent complexes from peripheral blood
    measure
    Topotecan-induced Stabilization of Topoisomerase I-DNA Covalent Complexes
    time Frame
    Up to 7 months
  10. description
    Plasma trough levels will be obtained weekly through the first cycle to provide a steady-state assessment. Steady-state plasma concentrations will be calculated for each patient. Exploratory correlative studies between veliparib exposure (plasma and bone marrow) with pharmacodynamic (biological endpoints, toxicity and efficacy) will be analyzed using nonparametric statistics. Significance for comparisons will be at the p \< 0.05 level.
    measure
    Pharmacokinetic Sampling Studies Measured Using a Validated Liquid Chromatography/Tandem Mass Spectrometric Method in Plasma and Bone Marrow
    time Frame
    Pre-treatment, day 1, day 8, day 14, day 15, and day 22 (approximately 24 hours post last dose)
Full study description
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.
detailed 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.
Source references
references
  1. citation
    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
    type
    DERIVED
Source notices and limitations
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    Preserved source evidence · Not medical advice