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ABT-888 and Cyclophosphamide in Treating Patients With Solid Tumors or Lymphoma That Did Not Respond to Previous Therapy
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
First Received: December 17, 2008   Last Updated: August 11, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00810966
  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: ABT-888
Drug: cyclophosphamide
Other: immunologic technique
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label
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 Cancer Institute (NCI):

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: 36
Study Start Date: December 2008
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00810966

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Robert J. Morgan, MD     626-256-4673 ext. 65928     rmorgan@coh.org    
City of Hope Medical Group Recruiting
Pasadena, California, United States, 91105
Contact: Mark V. McNamara, MD     626-396-2900     mmcnamara@ccsmg.com    
University of California Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: David R. Gandara, MD     916-734-3700     david.gandara@ucdmc.ucdavis.edu    
USC/Norris Comprehensive Cancer Center and Hospital Recruiting
Los Angeles, California, United States, 90033
Contact: Heinz-Josef Lenz, MD     323-865-3900     lenz_h@ccnt.usc.edu    
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Clinical Trials Office - Penn State Cancer Institute at Milton     717-531-3779     CTO@hmc.psu.edu    
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Clinical Trials Office - UPMC Cancer Centers     412-647-8073        
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000629899, NCI-09-C-0048, P8437
Study First Received: December 17, 2008
Last Updated: August 11, 2009
ClinicalTrials.gov Identifier: NCT00810966     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Leukemia, Lymphoid
Immunologic Factors
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Mantle Cell Lymphoma
Sezary Syndrome
Lymphoma, B-Cell, Marginal Zone
Cyclophosphamide
Mycosis Fungoides
Lymphoblastic Lymphoma
Follicular Lymphoma
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Lymphoma, B-Cell
Leukemia
Mycoses
Cutaneous T-cell Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-cell
Leukemia, B-cell, Chronic
Alkylating Agents
Hodgkin Disease
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphomatoid Granulomatosis
Immunoproliferative Disorders
Hodgkin Lymphoma, Adult

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

ClinicalTrials.gov processed this record on September 03, 2009