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

Lymphoma Clinical Trial

Official title:

A Phase I Study of ABT-888 in Combination With Metronomic Cyclophosphamide in Adults With Refractory Solid Tumors and Lymphomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00810966
• Other study ID #: 090048, CDR0000629899
• Secondary ID: NCI-09-C-0048P84
• Status: Active, not recruiting
• Phase: Phase 1
• First received: December 17, 2008
• Last updated: September 29, 2011
• Start date: December 2008

Study information

• Verified date: September 2011
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• cyclophosphamide

• veliparib

Other:
• immunologic technique

• laboratory biomarker analysis

• liquid chromatography

• mass spectrometry

• pharmacological study

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	City of Hope Medical Group	Pasadena	California
United States	UPMC Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	University of California Davis Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide			Yes
Primary	Safety			Yes
Secondary	Pharmacokinetics of ABT-888			No
Secondary	Clinical response			No
Secondary	Level of PARP inhibition			No
Secondary	Amount of ?-H2AX induction			No