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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide

Safety Issue:

Yes

Principal Investigator

Shivaani Kummar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Food and Drug Administration

Study ID:

090048, CDR0000629899

NCT ID:

NCT00810966

Start Date:

December 2008

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • cutaneous B-cell non-Hodgkin lymphoma
  • stage III cutaneous T-cell non-Hodgkin lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Neoplasms

Name

Location

UPMC Cancer Center at Magee-Womens HospitalPittsburgh, Pennsylvania  15213-3180
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
University of California Davis Cancer CenterSacramento, California  95817
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182
City of Hope Medical GroupPasadena, California  91105