GM-CSF and Rituximab After Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Follicular Non-Hodgkin Lymphoma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Biological: filgrastim Biological: rituximab Biological: sargramostim Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of GM-CSF (Sargramostim) and Rituximab Following Autologous Transplantation For Relapsed Follicular Lymphoma |
- Progression-free survival rate at 2 years after autologous stem cell transplantation (ASCT) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Toxicity as assessed by NCI CTCAE version 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Effects of sargramostim (GM-CSF) on the relative expression of activating and inhibitory FcγR on circulating monocytes and circulating dendritic cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Effects of GM-CSF on the level of circulating FcγR [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Immune effector cell reconstitution after ASCT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Enrollment: | 14 |
| Study Start Date: | October 2007 |
| Estimated Study Completion Date: | October 2013 |
| Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: GM-CSF and Rituximab After Autologous Stem Cell Transplant
Patients with relapsed or primary refractory FL who have received three or fewer prior antilymphoma regimens, who have achieved a CR or PR to their last anti-lymphoma therapy, and who have minimum of 2 x 106 CD34+ cells/kg cryopreserved and available for hematopoietic stem cell support will be considered for this study. High-dose therapy will consist of the BEAM regimen, supported by autologous peripheral blood progenitor cells. Day "0" is defined as the day of stem cell infusion. Beginning approximately 7-10 weeks after ASCT (day +49 to +70), patients will be treated with a 4-week course of GM-CSF and rituximab. GM-CSF will be administered three times per week for 8 weeks. Rituximab will be administered weekly for 4 weeks, beginning within 3 days after the first dose of GM-CSF. A second identical course of GM-CSF and rituximab will be administered beginning approximately 22-26 weeks after ASCT (day +154 to +182). |
Biological: filgrastim Biological: rituximab Biological: sargramostim Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation |
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.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Principal Investigator: | Craig Moskowitz, MD | Memorial Sloan-Kettering Cancer Center |
| Principal Investigator: | Matthew Matasar, MD | Memorial Sloan-Kettering Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Memorial Sloan-Kettering Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00521014 History of Changes |
| Other Study ID Numbers: | 07-085, P30CA008748, MSKCC-07085, BRLX-MSKCC-07-085 |
| Study First Received: | August 24, 2007 |
| Last Updated: | March 4, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Memorial Sloan-Kettering Cancer Center:
|
recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Carmustine Melphalan Rituximab Cytarabine Etoposide Lenograstim |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Myeloablative Agonists |
ClinicalTrials.gov processed this record on May 19, 2013