Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT00667615

Last Updated: 2018-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2017-02-28

Brief Summary

The purpose of this study is to replace a drug with many side effects, procarbazine, with a new novel drug, vorinostat, in a drug combination for the treatment of patients with diffuse large B-cell lymphoma. Vorinostat is the first of a new type of chemotherapy drug, known as a histone deacetylase inhibitor, to be approved by the Food and Drug Administration. It is approved for the treatment of certain lymphomas of the skin. It alters the cancer cell pathway by preventing cancer cells from reproducing. Vorinostat will be added to a combination of four other effective chemotherapy drugs that have been used for many years for the treatment of diffuse large B-cell lymphoma: rituximab, cyclophosphamide, etoposide and prednisone. The doses of vorinostat will be increased or decreased depending on the side effects that occur in each of the first few patients in the trial to find the safest dose with the least side effects. This is termed the phase I part of the clinical trial. Once the best dose of vorinostat is found, the rest of the patients in the clinical trial will be treated with this dose. This is termed the phase II part of the trial. The object of the trial is to find out what effects, good and/or bad, the combination of vorinostat, rituximab, cyclophosphamide, etoposide and prednisone will have on you and your lymphoma.

Conditions

Hodgkin's Disease; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

vorinostat in combination with cyclophosphamide, etoposide,prednisone and rituximab,peg-filgrastim or filgrastim

Group Type: EXPERIMENTAL

rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim

Intervention Type: DRUG

Patients will be treated with 6 cycles of rituximab, cyclophosphamide, etoposide, prednisone and vorinostat every 4 weeks. Quality of life determinations will be obtained at the beginning of each cycle of chemotherapy and at each visit during the first year of followup.

Interventions

rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim

Patients will be treated with 6 cycles of rituximab, cyclophosphamide, etoposide, prednisone and vorinostat every 4 weeks. Quality of life determinations will be obtained at the beginning of each cycle of chemotherapy and at each visit during the first year of followup.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• MSKCC or Weill Cornell biopsy confirmation of relapsed/refractory diffuse large B-cell lymphoma.Patients with large cell transformation of a low-grade B-cell lymphoma will be eligible.
• One or two prior chemotherapy regimens not including autologous stem cell transplantation.
• Age ≥ 60 years.
• Not a candidate for autologous stem cell transplantation.
• Patient must have performance status of ≤2 on the ECOG Performance Scale.
• Measurable disease
• Adequate organ and bone marrow function: ANC ≥ 1000/mm3, platelet count ≥ 50,000/mm3, total bilirubin ≤ 1.5 ULN (with exception of Gilbert's disease), AST/ALT ≤ 2.5 ULN, creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 ml/min, potassium and magnesium within normal limits.
• Male patients agree to use an adequate method of contraception for the duration of the study.
• Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.

Exclusion Criteria

• Patient who has had chemotherapy, radiotherapy, or biological therapy [including growth factors], within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) or who has not recovered from adverse events due to agents administered more than 30 days earlier. Patients on a stable dose of steroids for at least 4 weeks prior to onset of study therapy may be included.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s).
• Patient had prior treatment with an HDAC inhibitor (e.g., romidespin (Depsipeptide),NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103,CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
• Patients with active CNS lymphoma and/or lymphomatous meningitis are excluded. However, patients with a history of CNS lymphoma and/or lymphomatous meningitis who have been stable without evidence of CNS and/or leptomeningeal recurrence would be eligible. They must be off steroids or on a stable dose of steroids.
• Patient with a primary central nervous system lymphoma.
• Patient has known hypersensitivity to the components of study drug or its analogs.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
• Patient is expecting to father children within the projected duration of the study.
• Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
• Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
• Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
• Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.
• Patient is HIV +.
• Patient has active hepatitis B or C.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Endeavor Health

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Straus, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center @ BaskingRidge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center @ Phelps

Sleepy Hollow, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

08-045

Identifier Type: -

Identifier Source: org_study_id