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Adult Acute Megakaryoblastic LeukemiaPhase 1NCT00588991

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

A Phase 1 study testing Carboplatin, Laboratory Biomarker Analysis and Topotecan Hydrochloride in people with Adult Acute Megakaryoblastic Leukemia and Adult Acute Monoblastic Leukemia, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Laboratory Biomarker Analysis and Topotecan Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
4 Feb 2008to 16 Nov 2016
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • 5-19% 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
  • Bilirubin =< 2.0 mg/dL
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • LVEF >= 45% by MUGA or ECHO
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after completion of study therapy
  • No active disseminated intravascular coagulation
  • No active uncontrolled infection
  • Patients with infection that is under active treatment and controlled with antibiotics are eligible
  • No other life-threatening illness
  • No mental deficits and/or psychiatric history that would preclude giving informed consent or following protocol
  • No prior or current seizure disorder or a history of seizure
  • No more than 3 prior cytotoxic regimens
  • At least 3 weeks since prior cytotoxic chemotherapy
  • At least 2 weeks since prior radiotherapy
  • At least 4 weeks since prior autologous or allogeneic stem cell transplantation
  • No active graft-versus-host disease
  • At least 1 week since prior biologic therapies, including hematopoietic growth factors
  • At least 24 hours since prior hydroxyurea, steroids, imatinib mesylate, arsenic trioxide, interferon, or other noncytotoxic agents for blast count control
  • No prior ABT-888
  • No other concurrent chemotherapy, radiotherapy, or immunotherapy
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies for this cancer

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I Study of ABT-888 in Combination With Topotecan Plus Carboplatin for High-Risk Myeloproliferative Disorders and AML Out of Myeloproliferative Disorders

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility, tolerability, and toxicities of ABT-888 (veliparib) when administered alone and in combination with topotecan hydrochloride with or without carboplatin in patients with relapsed or refractory acute leukemia, high-risk myelodysplasia, or aggressive myeloproliferative disorders.

II. To determine the maximum tolerated dose of ABT-888 when administered with topotecan hydrochloride and carboplatin in these patients.

III. To determine if ABT-888 when administered with topotecan hydrochloride and carboplatin can induce clinical responses in these patients.

SECONDARY OBJECTIVES:

  1. To determine the pharmacokinetics of ABT-888 when administered alone and in combination with topotecan hydrochloride with or without carboplatin in these patients.

II. To obtain pharmacodynamic data regarding the ability of ABT-888 to inhibit poly (ADP-ribose) levels in leukemic blasts.

III. To obtain descriptive data regarding the mutational status and/or methylation status of key genes in selected DNA repair pathways (Fanconi complementation groups A-F, Blooms, and ataxia-telangiectasia) in leukemic blasts.

OUTLINE: This is a multicenter, dose-escalation study of veliparib.

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.

Patients undergo blood sample collection periodically for pharmacokinetic studies.

After completion of study therapy, patients are followed for 30 days.

Being tested
Carboplatin, Laboratory Biomarker Analysis, Topotecan Hydrochloride, Veliparib
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative study

  • Topotecan HydrochlorideDrug

    Also called Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride

    Given IV

  • VeliparibDrug

    Also called ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

    Given orally

Study groups in NCT00588991
Study groupRoleWhat they receive
Treatment (veliparib, topotecan hydrochloride, carboplatin)ExperimentalPatients 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.
Receives: Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Topotecan Hydrochloride; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 63 days

  2. Clinical response (CR, CRi, PR)

    Measured: Up to 3 years

Secondary outcomes (1)

  1. Pharmacokinetics and pharmacodynamics of veliparib

    Relevant individual PK parameters will be estimated using non-compartmental PK methods. PK parameters will be compared when administered alone or in combination by a paired student's t-test. Comparison of PK parameters among dose levels will be performed using non-parametric statistical methods for K-independent samples. Associations between exposure parameters (Cmax and AUC) and pharmacodynamic endpoints (cellular PAR levels, mutation and/or altered expression of selected DNA repair genes) will be assessed using the appropriate non-parametric statistical tests.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2008 (estimated)
  2. Study start4 Feb 2008
  3. Primary completion1 Nov 2016
  4. Study completion16 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00588991
Sponsor's protocol ID
NCI-2009-00259
Other IDs
NCI-2009-00259, CDR0000579626, J0783, 7968, P30CA006973, U01CA062491, U01CA069912, U01CA070095
Status last verified
Mar 2025
First submitted
20 Dec 2007
Last updated
2 Apr 2025
Results posted
No

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