GM-CSF, Rituximab, and Combination Chemotherapy in Treating Patients With Previously Untreated Advanced Follicular Non-Hodgkin Lymphoma
Conditions
Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, Follicular - Lymphoma, Non-Hodgkin
Conditions: Keywords
stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: rituximab Type: Biological
Name: sargramostim Type: Biological
Name: cyclophosphamide Type: Drug
Name: doxorubicin hydrochloride Type: Drug
Name: prednisone Type: Drug
Name: vincristine sulfate Type: Drug
Name: gene expression analysis Type: Genetic
Name: gene rearrangement analysis Type: Genetic
Name: polymerase chain reaction Type: Genetic
Name: R-CHOP regimen Type: Other
Name: laboratory biomarker analysis Type: Other
Overall Status
Not yet recruiting
Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as GM-CSF, may cause the body to make more blood cells and help it recover from the side effects of rituximab and combination chemotherapy.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with rituximab and combination chemotherapy works in treating patients with previously untreated advanced follicular non-Hodgkin lymphoma.
Detailed Description
OBJECTIVES:

Primary

- To evaluate the overall objective tumor response rate (complete and partial response rates) in patients with previously untreated advanced follicular non-Hodgkin lymphoma treated with sargramostim (GM-CSF) and R-CHOP.

Secondary

- To evaluate the time to progression.

- To evaluate the overall survival.

- To evaluate the duration of response.

- To evaluate the time to next treatment.

- To evaluate the safety profile of GM-CSF in combination with R-CHOP.

- To evaluate the influence of FcγR polymorphisms on clinical response.

- To monitor FcγR expressing cells in peripheral blood during treatment.

- To monitor the molecular biological marker bcl-2 [t(14;18)] in peripheral blood and bone marrow by quantitative PCR assay.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone on days 1-5. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) on days 2-6. Treatment repeats every 21 days for up to 6 courses. Patients then receive rituximab IV on day 1 and GM-CSF SC on days 1-5. Treatment with rituximab and GM-CSF repeats every 21 days for 2 courses. Patients achieving complete or partial response proceed to maintenance therapy.

- Maintenance therapy: Patients receive rituximab IV on day 1 and GM-CSF SC on days 1-5. Treatment repeats every 2 months for 12 courses.

Blood and bone marrow samples are collected at baseline and periodically during study for analysis of FcγR expression by immunophenotyping and bcl-2 rearrangement by quantitative PCR.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 4 years.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: DISEASE CHARACTERISTICS:

- Histologically confirmed follicular non-Hodgkin lymphoma

- Grade 1-3a disease

- Advanced disease

- Has undergone initial lymph node biopsy within the past 4 months

- At least 1 measurable lesion

- Bulky disease, as defined by the following GELF criteria:

- Nodal or extranodal mass > 7 cm in its greatest diameter

- Involvement of ≥ 3 nodal sites (each with a diameter > 3 cm)

- B symptoms

- Elevated serum LDH or β2-microglobulin

- Splenic enlargement

- Compression syndrome

- Pleural and/or peritoneal effusion

- No transformation to high-grade follicular lymphoma (secondary to low-grade follicular lymphoma)

- No prior or concurrent CNS disease (i.e., CNS lymphoma or lymphomatous meningitis) NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- ANC ≥ 1,000/mm^3*

- Platelet count ≥ 100,000/mm^3*

- Hemoglobin ≥ 8.0 g/dL*

- Total bilirubin ≤ 2.0 mg/dL*

- AST ≤ 3 times upper limit of normal*

- Serum creatinine ≤ 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after completion of study treatment

- No known HIV infection

- No active hepatitis B or C infection

- No serious underlying medical condition that would preclude study participation (e.g., ongoing infection, uncontrolled diabetes mellitus, gastric ulcer, active autoimmune disease, or heart failure)

- No known sensitivity or allergy to murine products

- No other prior or concurrent malignancies except nonmelanoma skin cancer or adequately treated in situ cervical cancer

- No other co-existing medical or psychological condition that would preclude study participation or ability to give informed consent NOTE: *Unless abnormalities are related to lymphoma

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior treatment for follicular lymphoma, including steroids or radiotherapy

- More than 4 weeks since prior corticosteroids unless administered at a dose equivalent to < 20 mg/day of prednisone

- More than 28 days since prior major surgery (excluding lymph node biopsy)

- More than 30 days since prior treatment in a clinical trial
Location
Start Date
March 2009
Sponsors
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page