Clinical trial NCT00836173: Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: CARBOPLATIN
DEXAMETHASONE
DIFFUSE LARGE B-CELL LYMPHOMA
ETOPOSIDE
GALLIUM NITRATE
IFOSFAMIDE
PHASE II
RELAPSED OR REFRACTORY
RITUXIMAB
Lead sponsor: Loyola University
Sponsor class: OTHER
Collaborators: name: Genta Incorporated
First posted: 2009-02-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: 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)
timeFrame: 12 weeks
Secondary outcomes:
measure: 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.
timeFrame: 18 months
measure: To determine the toxicities of the regimen
timeFrame: approximately 12 weeks
measure: To investigate in vitro assays that may predict response to gallium based salvage chemotherapy
timeFrame: 18 months
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
state: Illinois
Study officials:
affiliation: Loyola University
name: Scott Smith, MD, PhD, FACP
role: PRINCIPAL_INVESTIGATOR
References: