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

Condition(s) targeted: Hodgkin's Disease; Lymphoma

Intervention: rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Memorial Sloan-Kettering Cancer Center

Official(s) and/or principal investigator(s):
David Straus, MD, Principal Investigator, Affiliation: Memorial Sloan-Kettering Cancer Center

Overall contact:
David Straus, MD, Phone: 212-639-8365

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.

Official title: A Multi-Center Phase I/II Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine the maximum tolerated dose (MTD) of vorinostat given orally for 10 days in combination with cyclophosphamide, etoposide, prednisone and rituximab for elderly patients with relapsed diffuse large B-cell lymphoma

Secondary outcome:

determine the complete response rate to rituximab and a combination of vorinostat with cyclophosphamide, etoposide, and prednisone in elderly pts with relapsed diffuse large B-cell lymphoma who aren't candidates for autologous stem cell transplantation.

To estimate the quality of life for these patients at baseline, during and at completion of treatment.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

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.

David Straus, MD, Phone: 212-639-8365

Memorial Sloan-Kettering Cancer Center @ BaskingRidge, Basking Ridge, New Jersey 07920, United States; Recruiting
David Straus, MD
David Straus, MD, Principal Investigator

Memorial Sloan-Kettering Cancer Center @ Suffolk, Commack, New York 11725, United States; Recruiting
David Straus, MD, Phone: 212-639-8365
Paul Hamlin, MD, Phone: 212-639-6143
David Straus, MD, Principal Investigator

Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States; Recruiting
David Straus, MD, Phone: 212-639-8365
Paul Hamlin, MD, Phone: 212-639-6143
David Straus, MD, Principal Investigator

Weill Cornell Medical Center, New York, New York, United States; Not yet recruiting
Rebecca Elstrom, MD, Phone: 212-746-2063

Memorial Sloan-Kettering Cancer Center @ Phelps, Sleepy Hollow, New York 10591, United States; Recruiting
David Straus, MD, Phone: 212-639-8365
David Straus, MD, Principal Investigator

Memorial Sloan-Kettering Cancer Center

Starting date: April 2008
Last updated: July 20, 2011