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

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase II Study Evaluating Three Cyslces of Ifosfamide, Carboplatin, Etoposide, and Rituximab (RICE) Followed by Two Cycles of Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma MA

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00836173
• Other study ID #: 200119
• Status: Withdrawn
• Phase: Phase 2
• First received: February 3, 2009
• Last updated: March 14, 2016
• Start date: July 2008
• Est. completion date: May 2012

Study information

• Verified date: March 2016
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Genta Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine CR rates of standard salvage chemotherapy with rituximab, ifosfamide, carboplatin and etoposide (RICE) for relapsed/refractory diffuse aggressive NHL followed by a novel regimen of gallium nitrate, rituximab, and dexamethasone (GARD)		12 weeks
Secondary	To determine progression-free survival and overall survival following an autologous stem cell transplant performed after the completion of the above regimen, as well as assessment of stem cell collection.		18 months
Secondary	To determine the toxicities of the regimen		approximately 12 weeks
Secondary	To investigate in vitro assays that may predict response to gallium based salvage chemotherapy		18 months