Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00001337
First received: November 3, 1999
Last updated: February 14, 2015
Last verified: February 2015

November 3, 1999
February 14, 2015
April 1993
March 2018   (final data collection date for primary outcome measure)
Overall response and PFS [ Time Frame: Time of progression ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00001337 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma
Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma

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.

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.

Secondary:

Assess PFS in bcl-2 + lymphomas treated with dose-adjusted EPOCH-R, and determine if it is significantly better than dose-adjusted EPOCH alone.

Obtain pilot information on the CR and PFS of dose-adjusted EPOCH with G-CSF in CD20 negative B cell lymphomas, anaplastic large cell lymphomas (ALCL) and peripheral T-cell lymphomas (PTCL).

Assess toxicity of dose-adjusted EPOCH-Rituximab with G-CSF in agressive lymphomas.

Characterize the patterns of mdr-1, bcl-2, MIB-1 and mutant p53 expression in previously untreated lymphoma patients.

Assess the effect of EPOCH-R on ovarian function and reserve in female patients with PMBL.

Eligibility:

Non-Hodgkin's lymphomas in the following categories: diffuse large B-cell to include

gray zone lymphoma and follicular center cell grade IIIB, anaplastic large cell, aggressive

T-cell lymphomas and Burkitt Lymphoma.

Patients greater than or equal to 12 years old.

Stages II, III, IV for all subtypes, and Stage I for bulky (> 5 cm) primary mediastinal

lymphomas or Burkitt Lymphoma.

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 318 patients will be enrolled on this protocol.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Diffuse Large B-Cell Lymphoma (DLBCL)
  • Primary Meidastinal Lymphoma
  • Burkitt Lymphoma
  • Anaplastic Large-Cell Lymphoma
  • Gray Zone Lymphoma
  • 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.
Experimental: Arm A
EPOCH-R every 3 weeks for 6 cycles.
Interventions:
  • Drug: EPOCH
  • Biological: Rituximab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
338
March 2019
March 2018   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

Non-Hodgkin's lymphomas in the following categories: diffuse large B cell to include gray zone lymphoma and follicular center cell grade IIIB, anaplastic large cell, and aggressive T-cell lymphomas and Burkitt Lymphoma.

Patients with evidence of an underlying low-grade lymphoma will not be eligible for this study. This includes patients who have both indolent and aggressive histologies in the same or different biopsy sites (e.g. large cell lymphoma in a node and follicular center cell lymphoma in the bone marrow).

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: Stages II, III, IV for all subtypes, and stage I bulky (greater than 5 cm) primary mediastinal B-cell lymphomas or Burkitt Lymphoma.

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 cervix cancer.

Ability to give informed consent.

Both
12 Years and older
No
Contact: Margaret Shovlin, R.N. (301) 594-6597 mshovlin@mail.nih.gov
Contact: Wyndham H Wilson, M.D. (301) 435-2415 wilsonw@mail.nih.gov
United States
 
NCT00001337
930133, 93-C-0133
Not Provided
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP