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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall objective tumor response rate

Safety Issue:

No

Principal Investigator

Jean-Francois Rossi, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hopital Lapeyronie-CHU Montpellier

Authority:

Unspecified

Study ID:

CDR0000637105

NCT ID:

NCT00896519

Start Date:

March 2009

Completion Date:

Related Keywords:

  • Lymphoma
  • 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
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin

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