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Randomized Phase III Study in Low Grade Lymphoma Comparing Maintenance Anti-CD20 Antibody Versus Observation Following Induction Therapy


Phase 3
18 Years
N/A
Not Enrolling
Both
Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Small Lymphocytic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Small Lymphocytic Lymphoma

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Trial Information

Randomized Phase III Study in Low Grade Lymphoma Comparing Maintenance Anti-CD20 Antibody Versus Observation Following Induction Therapy


PRIMARY OBJECTIVES:

I. To compare the response rate, time to progression, time to treatment failure, and
survival for patients with low grade lymphoma treated with the cyclophosphamide -
fludarabine regimen with a control arm consisting of standard treatment with CVP.

II. To determine the effect of maintenance with anti-CD20 (IDEC C2B8) on time to
progression, time to treatment failure, and survival and its effects on lymphocyte number,
subsets, and quantitative immunoglobulin levels over time.

OUTLINE: This a two step, stratified, randomized study. Patients are stratified for arms I
and II (step 1) by age (under 60 vs 60 and over), tumor burden (high vs low), histology
(follicular vs other), and B symptoms (present vs absent). After arms I and II have been
completed, patients are stratified in arms III and IV (step 2) by extent of residual disease
(minimal vs gross), histology (follicular vs other), and initial tumor burden.

ARM I (CLOSED AS OF 9/2000): Patients receive cyclophosphamide IV over 30-45 minutes on day
1 and fludarabine IV over 10-20 minutes on days 1-5. Treatment repeats every 28 days in the
absence of disease progression for a minimum of 4 courses and a maximum of 6 courses.

ARM II: Patients receive cyclophosphamide IV over 30-45 minutes and vincristine IV on day 1,
and oral prednisone on days 1-5. Treatment repeats every 21 days in the absence of disease
progression for a minimum of 6 courses and a maximum of 8 courses.

After completion of therapy on arm I or II, patients are randomized into step 2 of this
study comprising arms III and IV.

ARM III: Patients receive maintenance therapy with rituximab (IDEC-C2B8 monoclonal antibody)
IV weekly for 4 weeks. Courses repeat every 6 months for 2 years. Maintenance therapy begins
4 weeks after the last chemotherapy.

ARM IV: Patients undergo no maintenance therapy and are observed.

Patients are followed every 3 months for 2 years, every 6 months for the next 3 years, and
then annually thereafter.


Inclusion Criteria:



- Patients must have Stage III-IV (Ann Arbor classification) low-grade Non-Hodgkin's
lymphoma

- Baseline measurements and evaluations must be obtained within 4 weeks prior to
registration; all areas of disease (evaluable and measurable) should be recorded and
mapped out in order to assess response and uniformity of response to therapy; must
have at least one objective MEASURABLE disease parameter

- Radiographic findings are acceptable providing that clear-cut measurement can be
made

- Abnormalities on scans may be used to document the presence of disease for
staging purposes; a clearly defined, bidimensionally measurable defect or mass
measuring at least 2 cm in diameter on a radionuclide or a CT scan will be
acceptable as measurable disease

- An enlarged spleen extending at least 2 cm below the costal margin will
constitute measurable disease providing that no explanation other than
lymphomatous involvement is likely; for an enlarged liver to constitute the only
evident measurable disease parameter, liver biopsy proof of lymphoma in the
liver is required

- Patients must have a tissue diagnosis of low-grade malignant lymphoma obtained within
12 months prior to registration (according to the International Working Formulation)
as below:

- ML- small lymphocytic (Category A)

- ML-follicular-small cleaved (Category B)

- ML-follicular-mixed small cleaved and large cell (Category C)

- Patients having both diffuse and follicular architectural elements will be considered
eligible if the histology is predominantly follicular (i.e. >= 50% of the
cross-sectional area); if the interval since tissue diagnosis of low-grade malignant
lymphoma is > 12 months, diagnostic confirmation using either FNA or nodal biopsy is
required to confirm that the histology remains in one of the eligible categories

- Women of child bearing potential and sexually active males are strongly advised to
use an accepted and effective method of birth control

- No prior chemotherapy, radiotherapy, or immunotherapy

- No active, uncontrolled infections (afebrile for > 48 hours off antibiotics)

- No evidence of a previous or concurrent malignancy, with the exception of 1) treated
carcinoma in situ of the cervix, 2) treated squamous cell or basal cell skin cancer
OR 3) any other surgically cured malignancy from which the patient has been disease
free for at least 5 years

- ECOG performance status 0-1

- WBC > 3000/mm^3

- Plts > 100,000/mm^3

- Creatinine =< 1.5 mg/dl

- Bilirubin < 2.0 mg/dl

- LFTs =< 5x ULN (SGOT and Alkaline Phosphate)

- These lab values must be obtained within 4 weeks prior to protocol entry; patients
with documented marrow involvement at the time of registration are not required to
meet the hematologic parameters above

- Patient must give signed informed consent

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to treatment failure

Outcome Description:

This comparison will be made using a one-sided logrank test with a 5% type I error rate.

Outcome Time Frame:

From maintenance randomization to the earlier of progression or death, assessed up to 5 years

Safety Issue:

No

Principal Investigator

Howard Hochster

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02972

NCT ID:

NCT00003204

Start Date:

March 1998

Completion Date:

Related Keywords:

  • Stage III Grade 1 Follicular Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Small Lymphocytic Lymphoma
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215