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

Lymphoma Clinical Trial

Official title:

A Phase II Study of GM-CSF (Sargramostim) and Rituximab Following Autologous Transplantation For Relapsed Follicular Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00521014
• Other study ID #: 07-085
• Secondary ID: P30CA008748MSKCC
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2007
• Last updated: November 18, 2015
• Start date: October 2007
• Est. completion date: July 2013

Study information

• Verified date: November 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• filgrastim

• rituximab

• sargramostim

Drug:
• carmustine

• cytarabine

• etoposide

• melphalan

Procedure:
• autologous hematopoietic stem cell transplantation

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Rate	after autologous stem cell transplantation (ASCT). Disease progression is defined using International Workshop Criteria for non-Hodgkin lymphoma37 and is defined as: = 50% increase in products of diameters of any previously identified abnormal node or nodule AND/OR; appearance of any new lesions	up to 3 years	No