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

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Steroids

Drug Information available for: Cyclophosphamide Prednisone Vincristine sulfate Doxorubicin Doxorubicin hydrochloride Sargramostim Rituximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall objective tumor response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to treatment progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Time to next treatment [ Designated as safety issue: No ]
Safety profile [ Designated as safety issue: Yes ]
Influence of FcγR polymorphisms on clinical response and overall survival [ Designated as safety issue: No ]
Monitoring of FcγR expressing cells during treatment [ Designated as safety issue: No ]
Quantitative monitoring of the molecular biological marker bcl-2 in peripheral blood and bone marrow by PCR assay [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	March 2009
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896519

Sponsors and Collaborators

Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS

Investigators

Principal Investigator:

Jean-Francois Rossi, MD, PhD

Hopital Lapeyronie-CHU Montpellier

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00896519 History of Changes
Other Study ID Numbers:	CDR0000637105, GOELAMS-FL2008-RCHOP-GM, FL2008-RCHOP-GM, EUDRACT2007-007056-33, RECF0907
Study First Received:	May 8, 2009
Last Updated:	July 7, 2009
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on May 23, 2013