Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma

Burkitt Lymphoma Clinical Trial

Official title:

Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001337
• Other study ID #: 930133
• Secondary ID: 93-C-0133
• Status: Completed
• Phase: Phase 2
• Start date: May 8, 1993
• Est. completion date: May 24, 2024

Study information

• Verified date: June 13, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. EPOCH: Etoposide, VP-16, NSC-141540; Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629....

Description:

Background:

The treatment of the intermediate and aggressive non-Hodgkin's lymphomas in adults and children commonly induces complete responses in a sizable fraction of the treated population, and about 2/3 of the complete responders appear to have prolonged disease-free survival.

The present study assesses the activity and tolerability in previously untreated patients of a regimen of EPOCH infusional chemotherapy given intensively with G-CSF support.

Objectives:

Primary:

Assess complete response (CR) and progression-free survival (PFS) of dose-adjusted EPOCH-Rituximab (DA-EPOCH-R) with G-CSF in agressive B-cell lymphomas.

Eligibility:

Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma (MGZL) and primary mediastinal B cell lymphoma (PMBL).

Patients greater than or equal to 12 years old.

Any Stage for PMBL and MGZL.

No prior systemic chemotherapy.

HIV negative.

Design:

This study will estimate the complete response rate of a group of previously untreated patients and the extent to which EPOCH infusional drug delivery accompanied by a hematopoietic growth factor can increase the dose intensity of treatment.

Patients receive prednisone orally for 5 days, a 96 hour infusion of vincristine, doxorubicin, and etoposide, and a bolus of cyclophosphamide on day 5.

Cycles are repeated every 21 days for a total of 6-8 cycles.

Patients with CD20 expressing tumors (i.e. mature B-cell lymphomas) will also receive rituximab, the humanized monoclonal antibody against the CD20 receptor on day 1 of each cycle.

A total of 348 patients will be enrolled on this protocol.

Other known NCT identifiers

• NCT00018980

Recruitment information / eligibility

• Status: Completed
• Enrollment: 348
• Est. completion date: May 24, 2024
• Est. primary completion date: May 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

• INCLUSION CRITERIA:

Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell

lymphoma.

Diagnosis confirmed by staff of the Hematopathology Section, Laboratory of Pathology, NCI. Tissue blocks from patients treated in extramural sites must be forwarded to the NCI for analysis of bcl-2 by IHC and other markers within 1 month of study entry.

Patients greater than or equal to 12 years old.

Stage and Prognosis of Patients: Any stage for MGZL and PMBL.

No prior systemic chemotherapy. Patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome).

HIV negative.

Not pregnant or nursing.

Adequate major organ function [in adults: serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 ml/min; and in children serum CR less than or equal to age-adjusted normal (age 12 to 15 maximum serum creatinine 1.2 mg/dl and age greater than 15 maximum serum creatinine 1.5 mg/dl); bilirubin less than 1.5 mg/dl; ANC greater than 1,000 and platelets greater than 100,000) unless impairment is due to organ involvement by lymphoma or immune-mediated mechanism caused by lymphoma.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If MUGA is obtained, the LVEF should exceed 40%.

No other serious concomitant medical illnesses or uncontrolled active infection that would jeopardize the patient's ability to receive the regimen with reasonable safety.

No history of unrelated (non-lymphomatous) neoplasms within past 5 years other than non-melanoma skin cancer or in-situ cancer.

Ability to give informed consent.

Related Conditions & MeSH terms

• Anaplastic Large-Cell Lymphoma
• Burkitt Lymphoma
• Diffuse Large B-Cell Lymphoma (DLBCL)
• Gray Zone Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Non-Hodgkin
• Primary Mediastinal Large B-cell Lymphoma

Intervention

Drug:
• EPOCH
Combination chemotherapy given with Rituximab (EPOCH-R) IV every 3 weeks for 6 cycles.

Biological:
• Rituximab
Rituximab given on Day 1 of combination chemotherapy (EPOCH-R) every 3 weeks for 6 cycles.

Locations

Country	Name	City	State
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Holy Cross Hospital, Fort Lauderdale	Fort Lauderdale	Florida
United States	St. Luke's Roosevelt Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. doi: 10.1016/s0140-6736(75)91142-3. — View Citation

Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. doi: 10.7326/0003-4819-102-5-596. — View Citation

Lai GM, Chen YN, Mickley LA, Fojo AT, Bates SE. P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991 Nov 11;49(5):696-703. doi: 10.1002/ijc.2910490512. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response and PFS	The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) patients may experience an improved progression free survival with EPOCH-R compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival.	Time of progression
Secondary	Safety and Toxicity	the proportion of patients with adverse events leading to discontinuation of therapy	Initiation of study drug until 30 days after treatment

External Links

•   NIH Clinical Center Detailed Web Page