ABT-888 and Cyclophosphamide in Treating Patients With Solid Tumors or Lymphoma That Did Not Respond to Previous Therapy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by National Institutes of Health Clinical Center (CC).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00810966
First received: December 17, 2008
Last updated: September 29, 2011
Last verified: September 2011
  Purpose

RATIONALE: ABT-888 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with cyclophosphamide may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of ABT-888 when given together with cyclophosphamide in treating patients with solid tumors or lymphoma that did not respond to previous therapy.


Condition Intervention Phase
Leukemia
Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: cyclophosphamide
Drug: veliparib
Other: immunologic technique
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of ABT-888 in Combination With Metronomic Cyclophosphamide in Adults With Refractory Solid Tumors and Lymphomas

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide [ Designated as safety issue: Yes ]
  • Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of ABT-888 [ Designated as safety issue: No ]
  • Clinical response [ Designated as safety issue: No ]
  • Level of PARP inhibition [ Designated as safety issue: No ]
  • Amount of γ-H2AX induction [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2008
Detailed Description:

OBJECTIVES:

  • Establish the safety and tolerability of ABT-888 when administered in combination with metronomic cyclophosphamide in patients with refractory solid tumors or lymphoma.
  • Establish the maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide in these patients.
  • Evaluate the pharmacokinetics of ABT-888 when administered in combination with metronomic cyclophosphamide in these patients.
  • Evaluate the antitumor response in these patients.
  • Determine the effects of treatment on the level of PARP inhibition and γ-H2AX in blood and tumor samples from these patients.

OUTLINE: This is a multicenter, dose-escalation study of ABT-888.

Patients receive oral ABT-888 once daily for 7-21 days and oral cyclophosphamide once daily for 14 or 21 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Plasma samples are collected periodically for pharmacodynamic and pharmacokinetic analysis. Samples are analyzed for PAR concentration by immunoassay, γ-H2AX levels by immunocytochemistry, quantification of the γ-H2AX marker and co-localization markers via quantitative immunofluorescence analysis, and ABT-888 concentration by liquid chromatography/mass spectrometry.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor or lymphoid (e.g., lymphoma or chronic lymphocytic leukemia) malignancies

    • Refractory to standard therapy or no acceptable standard treatment options exists

      • Patients with lymphoid malignancies must have disease progression after standard therapy AND have either refused stem cell transplantation (SCT) or SCT is not indicated
  • No gliomas, symptomatic CNS metastases, or carcinomatous meningitis

    • Patients with a history of CNS metastases are eligible, at the discretion of the principal investigator, provided they have received treatment and their CNS metastatic disease status has remained stable for ≥ 3 months without requiring steroids or anti-seizure medications

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 3 months
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would preclude compliance with study requirements
  • No history of seizures
  • No gastrointestinal condition that may predispose patient to drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, or active peptic ulcer disease)
  • No ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)
  • At least 4 weeks since prior radiotherapy
  • At least 2 weeks since prior investigational agents administered as part of a phase 0 study
  • Prior ABT-888 as part of a single- or limited-dosing study (e.g., phase 0 study) allowed
  • Prior cyclophosphamide allowed
  • No concurrent protease inhibitors for HIV-positive patients
  • No other concurrent chemotherapy
  • No other concurrent investigational or commercial anticancer agents or therapies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810966

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033
City of Hope Medical Group
Pasadena, California, United States, 91105
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Pennsylvania
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
UPMC Cancer Center at Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00810966     History of Changes
Other Study ID Numbers: 090048, CDR0000629899, NCI-09-C-0048, P8437
Study First Received: December 17, 2008
Last Updated: September 29, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
unspecified adult solid tumor, protocol specific
recurrent adult T-cell leukemia/lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
refractory chronic lymphocytic leukemia
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
adult nasal type extranodal NK/T-cell lymphoma
Waldenstrom macroglobulinemia
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 23, 2014