GM-CSF, Rituximab, and Combination Chemotherapy in Treating Patients With Previously Untreated Advanced Follicular Non-Hodgkin Lymphoma

Sponsor

French Innovative Leukemia Organisation (Other)

Overall Status

Unknown status

CT.gov ID

NCT00896519

Collaborator

(none)

Enrollment

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Biological: sargramostim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Genetic: gene expression analysis Genetic: gene rearrangement analysis Genetic: polymerase chain reaction Other: R-CHOP regimen Other: laboratory biomarker analysis	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Multicenter, Non Randomized Phase II Study to Evaluate Antitumor Efficacy and Safety of GM-CSF (Sargramostim, Leukine®) Associated With RCHOP Chemotherapy and Rituximab (MabThera®) Maintenance in Patients With First-line Advanced Follicular Non Hodgkin's Lymphoma

Study Start Date :

Mar 1, 2009

Anticipated Primary Completion Date :

Mar 1, 2011

Outcome Measures

Primary Outcome Measures

Overall objective tumor response rate []

Secondary Outcome Measures

Time to treatment progression []
Overall survival []
Duration of response []
Time to next treatment []
Safety profile []
Influence of FcγR polymorphisms on clinical response and overall survival []
Monitoring of FcγR expressing cells during treatment []
Quantitative monitoring of the molecular biological marker bcl-2 in peripheral blood and bone marrow by PCR assay []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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