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Acute Lymphoblastic LeukemiaPhase 1NCT01139970

Veliparib and Temozolomide in Treating Patients With Acute Leukemia

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 3 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 clinical trial is studies the side effects and best dose of giving veliparib together with temozolomide in treating patients with acute leukemia. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
3 sitesUnited States
Study dates
4 Jun 2010to 1 Dec 2018
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically or cytologically confirmed diagnosis of one of the following:
  • Relapsed or refractory acute myeloid leukemia (AML); patients with acute promyelocytic leukemia t(15;17) must have failed tretinoin (ATRA), arsenic, and gemtuzumab ozogamycin to be eligible (patients should be refractory to all three agents-absence of durable hematologic response or relapse with complete remission [CR] duration of less than 6 months)
  • Relapsed or refractory pre-B- or T-cell acute lymphoblastic leukemia (ALL); patients with Philadelphia chromosome-positive (Ph+) ALL [t(9;22)] will be eligible provided that they have failed (intolerance/resistance) at least 2 different tyrosine kinase inhibitors (TKIs) or have a mutation associated with resistance to TKIs (T315I)
  • Chronic myelogenous leukemia (CML) in accelerated or blastic phase; patients failed (resistance/intolerance) at least 2 different TKIs or have a mutation associated with resistance to TKIs (T315I)
  • Chronic myelomonocytic leukemia-2 (CMML-2) defined as having > 10% blasts (including promonocytes) in the bone marrow or > 5-19% blasts (including promonocytes) in the peripheral blood
  • AML arising in the setting of antecedent myelodysplasia (MDS) or myeloproliferative disorder (MPD)
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  • Therapy-related AML
  • Untreated AML in adults 60 years of age and older who are not candidates for induction chemotherapy due to poor-risk features including adverse cytogenetics or molecular markers (fms-related tyrosine kinase 3 [FLT3] internal tandem duplication [ ITD]+), or are unwilling to receive intensive induction chemotherapy; adverse cytogenetics: complex karyotype (>= 3 chromosomal abnormalities), 5q-, 7q-, 9q-, 20q-, abn12p, +21, +8, t(6;9), t(6;11), t(11;19), -7, -5, inv3/t(3;3), abn11q23, abn17p, abn21q
  • Untreated ALL in adults 60 years of age and older who are not candidates for induction chemotherapy due to poor-risk features including adverse cytogenetics [t(4;11); t(1;19), hypodyploidy] or are unwilling to receive intensive induction chemotherapy; patients with Ph+ ALL [t(9;22)] will be eligible provided that they have failed (intolerance/resistance) at least 2 different TKIs or have a mutation associated with resistance to TKIs (T315I)
  • Previous therapy
  • Only patients who have received or are ineligible for established curative regimens, including stem cell transplantation when applicable, can be enrolled on this study
  • Patients may have received any number of prior chemotherapy regimens, which may include allogeneic or autologous transplantation, provided that performance status and organ function are maintained
  • Previous cytotoxic chemotherapy should have been completed at least 3 weeks and radiotherapy at least 2 weeks prior to treatment on the study (6 weeks if the last regimen included carmustine [BCNU] or mitomycin C) and all adverse events (excluding alopecia, acne, rash) due to agents administered more than 3 weeks earlier should recover to =< grade 1; patients with hematologic malignancies are expected to have hematologic abnormalities at study entry; these abnormalities which are thought to be primarily related to the underlying leukemia, are not considered to be toxicities (AE) and do not need to resolve to =< grade 1
  • Patients should stop taking all biologic agents including hematopoietic growth factors, imatinib or similar TKIs, at least 1 week prior to treatment on the study and all adverse events (excluding alopecia, acne, rash) due to agents administered more than 1 week earlier should recover to =< grade 1; since only patients with advanced Ph+ ALL and CML in accelerated/blast phase are eligible for this study, this short period off TKIs was selected to avoid rapid leukemia progression; if using hydroxyurea, corticosteroids, or leukopheresis for blast count control, patients must be off >= 24 hrs before starting treatment on the study
  • Patients who have undergone autologous stem cell transplantation (ASCT) are eligible provided that they are >= 4 weeks from stem cell infusion and meet other eligibility criteria
  • Patients who have undergone allogeneic SCT (alloSCT) are eligible if they are >= 60 days post stem cell infusion, have no evidence of graft vs. host disease, and are >= 2 weeks off all immunosuppressive therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Patients have to be able to swallow pills
  • Total or direct bilirubin < 2 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 5 X institutional upper limit of normal
  • Creatinine < 2 mg/dl
  • Female patients of childbearing potential must have a negative pregnancy test
  • Female patients of childbearing potential and men 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 30 days afterward; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients may not be receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy
  • Any previous treatment with temozolomide
  • Patients with active central nervous system leukemia are excluded from this clinical trial because they may develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with a history of central nervous system (CNS) leukemia but no active disease at the time of enrollment are eligible
  • Hyperleukocytosis with > 30,000 blasts/ul; (if using hydroxyurea, corticosteroids, or leukopheresis for blast count control, patients must be off >= 24 hrs before starting treatment on the study); once patient starts treatment on the study the hydroxyurea use should be avoided, however, for patients with rapidly proliferating disease use of hydroxyurea is allowed on treatment days 1 through 12 if it becomes necessary to control a rising white blood cell (WBC) or leukostasis; the WBC need not reach 30,000/ul to start hydroxyurea during protocol days 1-12; the decision to start hydroxyurea during this time is at the discretion of the treating physician
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or temozolomide used in this study
  • Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
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  • Uncontrolled intercurrent illness including, but not limited to, 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; breastfeeding should be discontinued if the mother is treated with ABT-888
  • Known human immunodeficiency virus (HIV) infected patients (HIV testing will not be performed as a part of screening) on combination antiretroviral therapy, exclusive of zidovudine or starvudine, or HIV infected patients not on or willing to suspend antiretroviral therapy will be eligible provided that their cluster of differentiation (CD)4 cell count is greater than 250/mm3; HIV infected patients with CD4 count equal or less than 250/mm3 will be excluded

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: A Phase I Study of the PARP Inhibitor ABT-888 in Combination With Temozolomide in Acute Leukemias

This phase I clinical trial is studies the side effects and best dose of giving veliparib together with temozolomide in treating patients with acute leukemia. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, 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 temozolomide may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the maximum-tolerated dose (MTD) and recommended phase II dose of ABT-888 (veliparib) administered in combination with temozolomide in patients with acute leukemias.

II. To evaluate the feasibility, safety, and toxicity of administering ABT-888 in combination with temozolomide in patients with acute leukemias.

SECONDARY OBJECTIVES:

  1. To document response in acute leukemias. II. To observe the pharmacokinetics of both ABT-888 and temozolomide when administered alone and in combination.

III. To study the pharmacodynamics to determine the levels of poly(ADP-ribose) (PAR) before and after administration of ABT-888 and temozolomide in patient leukemia blasts, to analyze methyl-guanine methyl-transferase (MGMT) protein levels in primary leukemia blasts, and to quantify the induction of gamma-H2A histone family, member X (y-H2AX) and RAD51 recombinase (RAD51) foci in patient leukemia blasts after treatment.

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

Patients receive veliparib orally (PO) once daily (QD) on day 1 and twice daily on days 4-12 and temozolomide PO QD on days 3-9 of course 1.

Beginning at least 30 days after the start of treatment, patients receive veliparib PO twice daily (BID) on days 1-8 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients achieving complete remission receive 5 more courses in the absence of disease progression or unacceptable toxicity.

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

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Temozolomide, Veliparib
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Burkitt Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    Given PO

  • VeliparibDrug

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

    Given PO

Study groups in NCT01139970
Study groupRoleWhat they receive
Treatment (temozolomide and veliparib)ExperimentalPatients receive veliparib PO QD on day 1 and twice daily on days 4-12 and temozolomide PO QD on days 3-9 of course 1. Beginning at least 30 days after the start of treatment, patients receive veliparib PO BID on days 1-8 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission receive 5 more courses in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temozolomide; Drug: Veliparib

What is being measured

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

  1. MTD of veliparib, determined according to incidence of dose limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Measured: 28 days

Secondary outcomes (7)

  1. Response rate at the MTD, assessed using revised International Working Group response criteria

    The proportion of responders will be estimated and reported with the corresponding 90% confidence interval.

    Measured: Up to 30 days

  2. Changes in levels of poly(ADP-ribose) (PAR)

    The proportion of subjects with significant inhibition will be estimated for each dose level. Summary statistics and results of the statistical tests for contingency tables will be reported.

    Measured: From baseline to 6 hours after drug administration on day 1 of course 1

  3. Average expression of MGMT

    Average expression of MGMT will be measured and classified as positive versus negative (less than 20% of mean value) for all patients regardless of the administered drug dose. We will use the Fisher's exact test for 2 x 2 tables to assess whether the lack of MGMT expression correlates with the response.

    Measured: Up to 30 days

  4. Average change from baseline level in y-H2AX foci

    The average change from baseline level in γ-H2AX and RAD51 foci will be estimated for all patients to assess whether increase in foci and response to treatment are associated. Assessed using a single group repeated measures analysis of variance (ANOVA) with 0.05 significance level.

    Measured: From baseline to 30 days

  5. Average change from baseline level in RAD51 foci

    The average change from baseline level in γ-H2AX and RAD51 foci will be estimated for all patients to assess whether increase in foci and response to treatment are associated. Assessed using a single group repeated measures ANOVA with 0.05 significance level.

    Measured: From baseline to 30 days

  6. Non-homologous end joining repair

    Repeated measures data structure will provide adequate power to estimate intra- and inter-patient variability.

    Measured: Up to 30 days

  7. Double strand break (DSB) repair

    The plausible relationship between change in DSB repair and clinical response will be examined using the Fisher's exact test.

    Measured: Up to 30 days

Timeline

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

  1. First posted9 Jun 2010 (estimated)
  2. Study start4 Jun 2010
  3. Primary completion15 Apr 2014
  4. Study completion1 Dec 2018

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
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01139970
Sponsor's protocol ID
NCI-2011-01457
Other IDs
NCI-2011-01457, CDR0000674355, GCC 0940, JHUJ1051, JHUJ1051; GCC 0940, 8456, N01CM00071, N01CM62201
Status last verified
Nov 2025
First submitted
8 Jun 2010
Last updated
20 Nov 2025
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temozolomide in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of veliparib, determined according to incidence of dose limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01139970.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.

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