Chemotherapy Plus Radiation Therapy in Treating Patients With Refractory or Relapsed Hodgkin's Lymphoma

December 17, 2015 updated by: Memorial Sloan Kettering Cancer Center

High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients with refractory or relapsed Hodgkin's lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Assess the efficacy of a high-dose chemoradiotherapy regimen in patients with refractory or relapsed Hodgkin's lymphoma.

OUTLINE: Patients are stratified into 1 of 3 treatment arms (0-1 adverse prognostic factors vs 2 adverse prognostic factors vs 3 adverse prognostic factors).

  • Arm I (0-1 adverse prognostic factors): Patients receive ifosfamide by 24 hour infusion on day 2. Carboplatin is administered on day 2. Etoposide IV is administered once daily on days 1-3. Patients then receive filgrastim (G-CSF) subcutaneously or IV on days 5-12. Patients receive another course of ICE chemotherapy 2-3 weeks after the first course.

Leukapheresis is performed once WBC reaches at least 3000/mm^3 and continues until enough peripheral blood stem cells are collected.

Patients who have never received prior radiotherapy will receive accelerated hyperfractionated total lymphoid irradiation (TLI) twice a day for 5 days (days -10 to -6). Cyclophosphamide IV is then administered on days -5 and 4. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2).

Patients who have had prior radiotherapy receive high dose chemotherapy. Cyclophosphamide IV is administered on days -6 and -5. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2.

Peripheral blood stem cells are infused 24-36 hours after high-dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

  • Arm II (2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I.

Apheresis is performed once WBC is greater than 3000/mm^3 and continues until enough cells are collected. The second course of ICE is then administered.

Ifosfamide is administered by 48 hour continuous infusion on days 1-2. Carboplatin is administered on day 3. Etoposide IV is administered every 12 hours for 3 doses beginning on day 1. Patients receive G-CSF on days 5-14.

Patients who have never received prior radiotherapy will receive accelerated hyperfractionated TLI for 5 days (days -10 to -6). Cyclophosphamide IV is then administered every 12 hours on days -5 to -2. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2).

Patients who have had prior radiotherapy receive high-dose chemotherapy. Cyclophosphamide IV is administered every 12 hours on days -6 to -3. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2.

Peripheral blood stem cells are infused 24-36 hours after high dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

  • Arm III (3 adverse prognostic factors): Patients receive cyclophosphamide IV daily for 2 days, then G-CSF beginning on day 4 until blood stem cells are collected.

Patients then undergo apheresis until enough cells are collected.

Patients receive high-dose chemotherapy. Ifosfamide IV is administered for 1 hour. Etoposide is administered by continuous infusion for 12 hours. Carboplatin IV is administered for 1 hour. Etoposide is again administered by continuous infusion for 12 hours. Treatment is repeated daily for 5 days.

Peripheral blood stem cells are reinfused 24-36 hours after the last dose of chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

Patients who have never received prior radiation will now receive accelerated hyperfractionated TLI twice daily for 5 days. Patients receive a second course of high dose chemotherapy 45-90 days after reinfusion of cells. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2.

Patients who have received prior radiation therapy receive a second course of high-dose chemotherapy. Carmustine IV is administered on day -7. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2.

Peripheral blood stem cells are reinfused 24-48 hours after completion of second course chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

Patients are followed every 3 months for the first 2 years, every 4 months during years 3-5, and every 6 months thereafter.

PROJECTED ACCRUAL: This study will accrue 80 patients within 4 years.

Study Type

Interventional

Enrollment (Actual)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed residual or relapsed Hodgkin's lymphoma following conventional dose standard chemotherapy

  • Presence of the following prognostic factors are allowed:

    • B symptoms (fever, weight loss, night sweats)
    • Extranodal disease
    • Complete remission of less than 1 year duration

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin less than 2.0 mg/dL unless history of Gilbert's disease
  • No chronic active or persistent hepatitis

Renal:

  • No history of chronic renal insufficiency
  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No myocardial infarction within the past 6 months
  • No unstable angina
  • No significant cardiac arrhythmias other than chronic atrial fibrillation
  • Ejection fraction at least 50%

Pulmonary:

  • DLCO at least 50%

Other:

  • No uncontrolled infection
  • HIV negative

  • At least 5 years since prior malignancy except:

    • Curatively treated cutaneous basal cell carcinoma
    • Carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Fertile women must use effective contraception

PRIOR CONCURRENT THERAPY:

  • Must have failed conventional dose standard chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
(0-1 adverse prognostic factors): Patients receive ifosfamide by 24 hour infusion on day 2. Carboplatin is administered on day 2. Etoposide IV is administered once daily on days 1-3. Patients then receive filgrastim (G-CSF) subcutaneously or IV on days 5-12. Patients receive another course of ICE chemotherapy 2-3 weeks after the first course.
Biological: filgrastim
Experimental: Arm II
(2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I
Biological: filgrastim
Experimental: Arm III
Arm III (3 adverse prognostic factors): Patients receive cyclophosphamide IV daily for 2 days, then G-CSF beginning on day 4 until blood stem cells are collected
Drug: carboplatin
Drug: cyclophosphamide
Radiation: radiation therapy
Drug: cytarabine
Drug: etoposide
Procedure: peripheral blood stem cell transplantation
Biological: filgrastim
Drug: melphalan
Drug: carmustine
Drug: ifosfamide
Procedure: bone marrow ablation with stem cell support

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response
Time Frame: 2 years
Determine the overall objective response. CR rate [as measured from the start of ICE, (or high dose CTX) to the end of transplant for those who receive it, or the end of ICE for those who do not].Complete response (CR): No evidence of Hodgkin's disease determined clinically, radiologically or pathologically when indicated
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Joachim Yahalom, MD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1998

Primary Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 25, 2016

Last Update Submitted That Met QC Criteria

December 17, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-071
  • CDR0000066714 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-G98-1480

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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