Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT ID: NCT00836173

Last Updated: 2016-03-16

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2012-05-31

Brief Summary

The purpose of this study is to find out what effects, good and/or bad; rituximab, ifosfamide, carboplatin and etoposide (RICE) followed by gallium nitrate, rituximab and dexamethasone (GARD) have on diffuse large B cell lymphoma.

This research is being done to try to find a more effective treatment for this type of cancer. We want to know whether treatment with rituximab, ifosfamide, carboplatin and etoposide (RICE) then followed by gallium nitrate, rituximab and dexamethasone (GARD) will improve survival.

Rituximab, ifosfamide, carboplatin and etoposide (RICE) are part of the usual treatment for diffuse large B-cell lymphoma.

Gallium nitrate, rituximab and dexamethasone (GARD) in lymphoma is experimental.

Detailed Description

This is a Phase 2 trial evaluating the efficacy of adding the combination of GaRD x 2 cycles following 3 cycles of the standard salvage regimen of RICE for the treatment of relapsed or refractory diffuse, large B-cell lymphoma (DLBCL). The study will include patients who have relapsed after 1 prior treatment regimen or who are refractory to initial chemotherapy. We will evaluate patients for response rate (both partial and complete), toxicities, as well as overall and progression free survival. Eligible patients will receive standard RICE x 3 cycles followed by GaRD x 2 cycles. Patients who would otherwise be eligible, may then proceed to autologous stem cell transplant (ASCT).

Conditions

Diffuse Large B-cell Lymphoma

Study Design

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

Study Groups

RICE followed by GARD

1. RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, for 3 cycles.

2. GaRD treatment: After RICE treatment, gallium nitrate will be given continuously over a 7 day period. In addition rituximab will be given on day 1 of each cycle. Dexamethasone will be given for the first 4 days of each cycle. The length of each cycle is 21 days.

Group Type: EXPERIMENTAL

RICE

Intervention Type: DRUG

RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, each cycle is 14 days (2 weeks). Patients will receive 3 cycles of RICE treatment.

GaRD Treatment

Intervention Type: DRUG

After RICE treatment, patients will have gallium nitrate IV through a vein continuously over a 7 day period. Patients will also receive rituximab by intravenous infusion over a 3-6 hour period on day 1 of each cycle. Dexamethasone will be given as pills to be taken for 4 days in a row on the first 4 days of each cycle. The length of each cycle is 21 days (3 weeks). All patients will have 2 cycles of GaRD.

Interventions

RICE

RICE treatment: Rituximab by intravenous infusion over 6-8 hours on day 1, Eptoposide by intravenous infusion over 2 hours on day 3-5, a 1-hour infusion of Carboplatin on day 4 and a 24-hour infusion of Ifosfamide on day 4, each cycle is 14 days (2 weeks). Patients will receive 3 cycles of RICE treatment.

Intervention Type: DRUG

GaRD Treatment

After RICE treatment, patients will have gallium nitrate IV through a vein continuously over a 7 day period. Patients will also receive rituximab by intravenous infusion over a 3-6 hour period on day 1 of each cycle. Dexamethasone will be given as pills to be taken for 4 days in a row on the first 4 days of each cycle. The length of each cycle is 21 days (3 weeks). All patients will have 2 cycles of GaRD.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Must have histologically or cytologically confirmed diffuse, large B-cell lymphoma (WHO classification diffuse large B-cell lymphoma or mediastinal large B-cell lymphoma), immunoblastic B cell lymphoma or Burkitts lymphoma. Transformed, large B-cell lymphoma will be excluded.
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with spiral CT scan.
• Must be refractory to initial therapy or have disease relapse from prior therapy and must be at least 3 weeks post treatment from prior chemotherapy or radiation therapy.
• Age >18 years.
• Life expectancy >24 weeks
• SWOG performance status <1 (Karnofsky >80%).
• Must have normal organ function (or impaired marrow function) as defined below:

• leukocytes > or equal to 1,500/mcL
• absolute neutrophil count >or equal to 1,000/mcL
• platelets >or equal to 50,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT)<or equal to 2.5 X institutional upper limit of normal unless due to lymphoma involvement
• creatinine clearance > than or equal to 60 mL/min
• Must agree not to become pregnant for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Follicular B-cell lymphomas, small lymphocytic lymphomas, chronic lymphocytic leukemia, lymphoblastic lymphomas and all T-cell lymphomas.
• Patients may not be receiving any other investigational agents, within trials in the previous 4 weeks.
• Patients with known CNS metastases are excluded from this clinical trial.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gallium nitrate, rituximab, dexamethasone, ifosfamide, carboplatin, and/or etoposide.
• Prior therapy with gallium nitrate, ifosfamide, carboplatin and/or etoposide
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and women who are nursing are excluded from this study.
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with RICE and/or GaRD.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genta Incorporated

INDUSTRY

Sponsor Role: collaborator

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Scott E Smith, MD, PhD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott Smith, MD, PhD, FACP

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, United States

Countries

United States

Other Identifiers

200119

Identifier Type: -

Identifier Source: org_study_id