GM-CSF and Rituximab After Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Follicular Non-Hodgkin Lymphoma

NCT ID: NCT00521014

Last Updated: 2015-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2013-07-31

Brief Summary

RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant helps stop the growth of cancer cells by stopping them from dividing or by killing them. An autologous stem cell transplant may be able to replace the blood-forming cells that were destroyed by chemotherapy. GM-CSF may increase the number of immune cells found in bone marrow or peripheral blood. Giving a monoclonal antibody, such as rituximab, after the transplant may find any remaining cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving GM-CSF together with rituximab after autologous stem cell transplant may be an effective treatment for follicular non-Hodgkin lymphoma.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with rituximab after autologous stem cell transplant works in treating patients with relapsed or primary refractory follicular non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To assess the progression-free survival rate at 2 years after autologous stem cell transplantation (ASCT) in patients with relapsed or primary refractory follicular lymphoma treated with sargramostim (GM-CSF) and rituximab after ASCT.

Secondary

• To assess the safety of administering GM-CSF and rituximab after ASCT.
• To assess the effects of GM-CSF on the relative expression of activating and inhibitory FcγR on circulating monocytes.
• To assess the effects of GM-CSF on the relative expression of activating and inhibitory FcγR on circulating dendritic cells.
• To assess the effects of GM-CSF on the level of circulating FcγR.
• To assess the reconstitution of NK cells, NK-T cells, dendritic cell subsets, and regulatory T-cells after ASCT.

OUTLINE:

• High-dose chemotherapy: Patients receive carmustine IV over 2 hours on day -7, etoposide IV over 1 hour and cytarabine IV every 12 hours on days -6 to -3, and melphalan IV on day -2.
• Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously (SC) once a day beginning on day 5 and continuing until blood counts recover.
• Sargramostim (GM-CSF) and rituximab: Beginning approximately 7-10 weeks (49-70 days) after ASCT, patients receive GM-CSF SC 3 times a week for 8 weeks and rituximab IV once weekly for 4 weeks (beginning within 3 days after the first dose of GM-CSF). Patients receive a second course of GM-CSF and rituximab (as above) beginning approximately 22-26 weeks (154-182 days) after ASCT.

After the completion of study treatment, patients are followed periodically for 2 years.

Conditions

Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma

Study Design

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

Study Groups

GM-CSF and Rituximab After Autologous Stem Cell Transplant

GM-CSF: 250 mcg (flat dose) three times per week for 8 weeks, administered on alternate days. Thus, 24 doses of GM-CSF will be administered.

Rituximab: 375 mg/m2/week for 4 weeks, beginning within 3 days after the first dose of GM-CSF; rituximab. The second course of GM-CSF and rituximab will be administered approximately 22-26 weeks (day +154 to +182) after ASCT.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologic diagnosis of grade 1, 2, 3, or transformed follicular lymphoma
• Achieved a complete or partial response to last salvage therapy

• Completed salvage therapy within the past 12 weeks
• No disease progression since last salvage therapy
• One of the following disease statuses must have been present prior to receiving salvage therapy

• Refractory to last anti-lymphoma therapy
• Last remission duration less than 1½ years if salvage therapy is 3rd regimen
• Last remission duration less than 3 years if salvage therapy is 2nd regimen
• Minimum of 2 x 10^6 CD34+ cells/kg cryopreserved and available for hematopoietic stem cell support
• No leptomeningeal disease or brain parenchyma involvement

PATIENT CHARACTERISTICS:

• Cardiac ejection fraction > 50%

• If over 60 years of age, no evidence of cardiac ischemia by treadmill stress test (stress echo or sesta-MIBI)
• Adjusted diffusing capacity ≥ 50% of the predicted value on pulmonary function testing
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 mL/min
• ANC > 1,000/μL
• Platelet count > 50,000/μL
• Total bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL if Gilbert's disease is suspected)
• Not pregnant or breast-feeding
• Fertile patients must use an acceptable form of birth control
• HIV I or II negative
• No acute or chronic hepatitis B
• No active hepatitis C
• No medical illness (unrelated to non-Hodgkin lymphoma), including malignancies that, in the opinion of the attending physician and/or principal investigator, would preclude study treatment
• No other malignancy within the past 5 years except curatively treated cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• No more than 3 prior anti-lymphoma regimens, inclusive of the salvage therapy

• Biologic agents (e.g., monoclonal antibodies and vaccines) administered as part of a planned treatment regimen will not be considered distinct regimens
• Chemotherapy administered primarily for the purpose of stem cell mobilization (e.g., cyclophosphamide at 2-4 g/m²) will not be considered an anti-lymphoma regimen
• No prior autologous or allogeneic hematopoietic stem cell transplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Moskowitz, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Matthew Matasar, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-07085

Identifier Type: -

Identifier Source: secondary_id

BRLX-MSKCC-07-085

Identifier Type: -

Identifier Source: secondary_id

07-085

Identifier Type: -

Identifier Source: org_study_id