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

Original Study ID : 08-045

NCT ID : NCT00667615

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

Official Title : 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)

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.

Source : Memorial Sloan-Kettering Cancer Center

Overall Status : Recruiting

Start Date : April 2008

End Date : April 2011

Completion Date : April 2011

Official Title : Phase 1/Phase 2

Phase : Interventional

Study Design : Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Enrollment : 59

Verification Date : March 2009

First Received Date : April 24, 2008

Trial Eligibility

Criteria :
Inclusion Criteria:

- MSKCC 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.

Gender : Both

Minimum Age : 60 Years

Maximum Age : N/A

Healthy Volunteers : No

Facilities

Facility Name : Memorial Sloan-Kettering Cancer Center @ BaskingRidge

Status : Recruiting

City : Basking Ridge

State : New Jersey

Zip Code : 07920

Country : United States

Facility Name : Memorial Sloan Kettering Cancer Center

Status : Recruiting

City : New York

State : New York

Zip Code : 10065

Country : United States

Facility Name : Memorial Sloan-Kettering Cancer Center @ Suffolk

Status : Recruiting

City : Commack

State : New York

Zip Code : 11725

Country : United States

Facility Name : Memorial Sloan-Kettering Cancer Center @ Phelps

Status : Recruiting

City : Sleepy Hollow

State : New York

Zip Code : 10591

Country : United States

OutComes

Primary OutComes

Measure : 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

Time Frame : conclusion of the study

Safety issue : Yes

Secondary OutComes

Measure : 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 transpl

Time Frame : conclusion of the study

Safety issue : Yes

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

Time Frame : conclusion of the study

Safety issue : No

Interventions

Type : Drug

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

Description : 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.

Clinical Trial Name - Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for