Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00003204
Other study ID # NCI-2012-02972
Secondary ID E1496U10CA021115
Status Completed
Phase Phase 3
First received May 2, 2000
Last updated February 26, 2013
Start date March 1998

Study information

Verified date February 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy followed by rituximab or observation in treating patients who have stage III or stage IV low-grade non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which regimen of combination chemotherapy, with or without rituximab, is more effective for non-Hodgkin's lymphoma


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 515
Est. completion date
Est. primary completion date May 2006
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

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


Related Conditions & MeSH terms

  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • 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

Intervention

Drug:
cyclophosphamide
Given IV
fludarabine phosphate
Given IV
vincristine sulfate
Given IV
prednisone
Given PO
Biological:
rituximab
Given IV
Other:
laboratory biomarker analysis
Correlative studies

Locations

Country Name City State
United States Eastern Cooperative Oncology Group Boston Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to treatment failure This comparison will be made using a one-sided logrank test with a 5% type I error rate. From maintenance randomization to the earlier of progression or death, assessed up to 5 years No
See also
  Status Clinical Trial Phase
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Terminated NCT00377104 - Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Phase 1
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1
Completed NCT00608361 - Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery Phase 1
Terminated NCT00288067 - Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma Phase 1/Phase 2
Completed NCT00118170 - Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function Phase 1
Completed NCT00098891 - MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas Phase 1
Completed NCT00004241 - 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma Phase 1
Terminated NCT00947388 - Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL) Phase 1
Terminated NCT00096005 - Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas Phase 1
Terminated NCT00101244 - SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma Phase 1
Completed NCT00105001 - Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer Phase 2
Completed NCT00040846 - Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies Phase 2
Completed NCT00112593 - Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer N/A
Completed NCT01129193 - AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma Phase 1
Withdrawn NCT01558778 - Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant N/A
Terminated NCT00354185 - PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma Phase 1
Terminated NCT01805037 - Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas Phase 1/Phase 2
Completed NCT01959477 - Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant Phase 0
Completed NCT01024010 - Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Phase 2