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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: melphalan

Drug: etoposide

Biological: sargramostim

Biological: rituximab

Biological: filgrastim

Drug: cytarabine

Procedure: autologous hematopoietic stem cell transplantation

Drug: carmustine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00521014

07-085

P30CA008748 (U.S. NIH Grant/Contract)

MSKCC-07085

BRLX-MSKCC-07-085

Details and patient eligibility

About

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.

Full 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.

Enrollment

14 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

14 participants in 1 patient group

GM-CSF and Rituximab After Autologous Stem Cell Transplant

Experimental group

Description:

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.

Treatment: