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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00521014
First received: August 24, 2007
Last updated: July 23, 2013
Last verified: July 2013
  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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
Study Completion Date: July 2013
Primary Completion Date: July 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
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521014

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
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: July 23, 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 April 17, 2014