Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Refractory Hodgkin's Disease or Non-Hodgkin's Lymphoma

August 15, 2018 updated by: Montefiore Medical Center

Phase II Study of Intensive Carmustine and Etoposide With Cisplatin or Cyclophosphamide, Followed By Rescue With Autologous Bone Marrow Treated In Vitro With Etoposide and/or Peripheral Blood Stem Cells Mobilized With Filgrastim (G-CSF) or Sargramostim (GM-CSF) With or Without Radiotherapy in Patients With Resistant Hodgkin's Disease or Non-Hodgkin's Lymphoma

RATIONALE: 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. Bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy to kill more cancer cells.

PURPOSE: This phase II trial is studying giving high-dose chemotherapy followed by bone marrow or peripheral stem cell transplantation to see how well it works in treating patients with refractory Hodgkin's disease or non-Hodgkin's lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the antitumor activity of intensive carmustine and etoposide with cisplatin or cyclophosphamide, followed by rescue with autologous bone marrow (ABM) treated in vitro with etoposide and/or peripheral blood stem cells mobilized with filgrastim (G-CSF) or sargramostim (GM-CSF) with or without radiotherapy in patients with refractory Hodgkin's disease or non-Hodgkin's lymphoma. II. Determine the time to recovery of peripheral blood counts in patients treated with this regimen. III. Correlate the rate of peripheral blood cell recovery in these patients with in vitro growth of ABM treated with etoposide.

OUTLINE: This is a multicenter study. Autologous bone marrow (ABM) is harvested and two-thirds of the ABM is treated in vitro with etoposide (VP-16). ABM may have been stored earlier in the course of the disease for patients who are at high risk of relapse or who were previously treated with agents causing bone marrow or stem cell damage (e.g., nitrosoureas, pelvic irradiation). Patients with prior bone marrow involvement and subsequent bone marrow remission must have received 1 or 2 additional courses of the same chemotherapy before undergoing harvest of ABM. Patients for whom PBSC rescue alone is planned also undergo ABM harvest in case back-up ABM rescue is needed. Patients then receive sargramostim (GM-CSF) or filgrastim (G-CSF) subcutaneously beginning 5 days before harvest of peripheral blood stem cells (PBSC) and continuing until completion of harvest. Patients without extensive prior radiotherapy undergo radiotherapy to areas of measurable active disease plus a 2 cm margin on days -21 to -17 and -14 to -8. Patients without a contraindication to cisplatin (e.g., hearing impairment, peripheral neuropathy) receive cisplatin IV over 3 hours on days -7 to -3 and carmustine IV over 2 hours and VP-16 IV over 4 hours on days -6 to -4. Patients with a contraindication to cisplatin receive cyclophosphamide IV every 12 hours, VP-16 IV over 1 hour every 12 hours, and carmustine IV over 1 hour on days -7 to -4. ABM and/or PBSC are reinfused on day 0. The first 6 ABM rescue patients receive untreated ABM and subsequent patients receive ABM treated in vitro with VP-16. Patients with bone marrow biopsy showing no evidence of regeneration (marrow cellularity less than 1%) at day 21 after PBSC rescue undergo back-up ABM rescue. Patients without engraftment (granulocyte count less than 500/mm3 and untransfused platelets no greater than 20,000/mm3) by day 28 after rescue with ABM treated in vitro with VP-16 undergo rescue with untreated ABM.

PROJECTED ACCRUAL: A total of 21-46 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

35

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
      • Bronx, New York, United States, 10461
        • Albert Einstein Comprehensive 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

15 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Diagnosis of resistant Hodgkin's disease Eligible subtypes: Lymphocytic predominance Nodular sclerosing Mixed cellularity Lymphocyte depleted Not otherwise specified Must meet 1 of the following conditions: Disease progression after at least 1 course of prior therapy on each of 2 regimens comprising combination chemotherapy or radiotherapy Less than a partial remission (PR) after at least 2 courses on each of 2 regimens Failure to achieve a complete remission (CR) after 6 courses of 1 or 2 regimens Relapse less than 1 year off initial therapy OR Diagnosis of intermediate- or high-grade non-Hodgkin's lymphoma (NHL) Eligible subtypes: Diffuse poorly differentiated lymphocytic Diffuse mixed lymphocytic-histiocytic Nodular histiocytic Diffuse histiocytic Diffuse undifferentiated Lymphoblastic Must meet 1 of the following conditions: Disease progression after 1 course of prior therapy Failure to achieve a PR after 2 courses of prior therapy Failure to achieve a CR after 6 courses of prior therapy OR Diagnosis of low-grade NHL Eligible subtypes: Diffuse well-differentiated lymphocytic Nodular poorly differentiated lymphocytic Nodular mixed lymphocytic-histiocytic Failure on second-line therapy administered for progressive symptomatic disease or organ compromise Measurable disease by physical exam, external imaging or scanning studies, or tumor markers No severe symptomatic CNS disease of any etiology History of prior CNS tumor allowed if no signs or symptoms at study entry Active CNS lymphoma (meningeal lymphomatosis) rendered disease-free by conventional therapies allowed Epidural metastases or discrete parenchymal brain lesions allowed if tumors can be encompassed in standard treatment fields Bilateral marrow core biopsy free of tumor and showing at least 30% cellularity Prior marrow involvement allowed if marrow is histologically normal at time of storage No significant skin breakdown due to tumor or other disease A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: Karnofsky 70-100% OR ECOG 0-1 Life expectancy: At least 8 weeks without transplantation Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 150,000/mm3 Hepatic: Bilirubin no greater than 1.8 mg/dL SGOT and SGPT less than 2 times normal No high risk for veno-occlusive disease of the liver Renal: No severe renal dysfunction unless due to tumor invasion Creatinine no more than 1.5 mg/dL Creatinine at least 60 mL/min Cardiovascular: No severe cardiovascular dysfunction unless due to tumor invasion No myocardial infarction within the past 6 months No symptoms of major heart disease Ejection fraction at least 50% by MUGA scan Essential hypertension controlled with medication allowed Pulmonary: No severe pulmonary dysfunction unless due to tumor invasion DLCO at least 50% normal No symptomatic obstructive or restrictive pulmonary disease Other: No insulin-dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No active infection HTLV-III negative (no AIDS-related complex)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas or mitomycin) Prior exposure to etoposide, cisplatin, or carmustine allowed if cumulative dose of chloroethylnitrosourea (carmustine or lomustine) no greater than 400 mg/m2 Prior doxorubicin or daunorubicin dose of 450 mg/m2 or more allowed if LVEF at least 50% No concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids for hypercalcemia allowed Radiotherapy: See Disease Characteristics No prior whole-pelvic radiotherapy Other prior radiotherapy allowed Surgery: Not specified Other: No concurrent nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for major ventricular arrhythmias

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: Randomized
  • Interventional Model: Parallel Assignment

Collaborators and Investigators

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

Sponsor

Montefiore Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Rasim Ahmet Gucalp, MD, Albert Einstein College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

April 1, 1988

Primary Completion (Actual)

July 1, 1991

Study Completion (Actual)

July 1, 1991

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

March 25, 2004

First Posted (Estimate)

March 26, 2004

Study Record Updates

Last Update Posted (Actual)

August 17, 2018

Last Update Submitted That Met QC Criteria

August 15, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8802027
  • P30CA013330 (U.S. NIH Grant/Contract)
  • AECM-8802027
  • NCI-V89-0089

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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