Combination Chemotherapy and Radiation Therapy in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed or Refractory Hodgkin's Lymphoma

December 22, 2015 updated by: Memorial Sloan Kettering Cancer Center

Risk-Adapted High Dose Chemoradiotherapy and Autologous Stem Cell Transplantation for Patients With Relapsed and Primary Refractory Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving combination chemotherapy and radiation therapy with an autologous stem cell transplant, using peripheral stem cells or bone marrow from the patient, may allow more chemotherapy to be given so that more cancer cells are killed. Giving combination chemotherapy together with radiation therapy before an autologous stem cell transplant may be an effective treatment for Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well combination chemotherapy and radiation therapy work in treating patients who are undergoing an autologous stem cell transplant for relapsed or refractory Hodgkin's lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine whether event-free survival of patients with low to high-intermediate risk, relapsed or refractory Hodgkin's lymphoma can be improved when treated with cytoreductive combination chemotherapy followed by radiotherapy, high-dose combination chemotherapy, and autologous stem cell transplantation.

Secondary

  • Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to risk factors (low or low-intermediate risk [0-1 risk factor] vs high-intermediate risk [2 risk factors]).

  • ICE-based cytoreductive chemotherapy: Patients are assigned to 1 of 2 treatment groups.

    • Group I (patients with low or low-intermediate risk disease): Patients receive ICE comprising ifosfamide IV and carboplatin IV once on day 2 and etoposide IV over 1 hour once daily on days 1-3. Patients then receive ifosfamide IV twice on day 15, carboplatin IV once on day 17 and etoposide IV over 1 hour twice daily on days 15-17.
    • Group II (patients with high-intermediate risk disease): Patients receive ifosfamide IV twice on days 1 and 17, carboplatin IV once on days 3 and 19, and etoposide IV over 1 hour twice daily on days 1-3 and 17-19.

In both groups, patients undergo stem cell collection after either the first or second OR first and second courses of ICE.

  • Stem cell mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until stem cell collection is completed. Patients undergo a maximum of 5 daily apheresis sessions. Patients who mobilize fewer than the required minimal number of stem cells repeat apheresis with high-dose G-CSF alone or undergo bone marrow harvest. Patients then proceed to radiotherapy, high-dose chemotherapy (HDC), and autologous stem cell transplant (ASCT) OR noncross-resistant chemotherapy based on response to ICE-based cytoreductive chemotherapy.
  • Restaging studies: Patients undergo restaging studies with CT scan and positron emission tomography (PET). Patients who are chemosensitive with a normal PET scan proceed to radiotherapy, HDC, and ASCT. Patients who progress on ICE, or who respond but have an abnormal PET scan, proceed to noncross-resistant chemotherapy comprising gemcitabine hydrochloride, vinorelbine, and doxorubicin HCl liposome (GND).
  • GND chemotherapy: Patients receive gemcitabine hydrochloride IV, vinorelbine IV, and doxorubicin HCl liposome IV on days 1, 15, 29, and 43. Patients then proceed to radiotherapy, HDC, and ASCT in the absence of disease progression.
  • Radiotherapy: Within 2 weeks after completion of the ICE or GND regimen, patients who have no history of prior radiotherapy receive radiotherapy according to stratification by disease extent (isolated lymph nodes vs ≥ 2 contiguous nodal-based masses with or without extensive small-volume lymphadenopathy vs extensive small-volume lymphadenopathy). These patients undergo either involved-field radiotherapy (IFRT) twice daily over 1-2 weeks, total lymphoid irradiation (TLI) twice daily over 1 week, or both concurrently.
  • HDCT: Patients who undergo TLI only OR IFRT and TLI receive high-dose cyclophosphamide IV twice daily and etoposide IV once daily on days -5 and -2. Patients who undergo IFRT only OR do not undergo radiotherapy receive high-dose cyclophosphamide IV twice daily and etoposide IV once daily on days -6 and -3 and carmustine IV once on day -2.
  • ASCT: Patients undergo ASCT or reinfusion of bone marrow, if harvested, on day -1 or 0. Patients then receive G-CSF beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 15 months.

Study Type

Interventional

Enrollment (Actual)

98

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, 10065
        • 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

18 years to 72 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologic diagnosis of Classical Hodgkin's Lymphoma. Lymphocyte predominant histology will be excluded.
  • Primary refractory or relapsed disease proven by biopsy or fine needle aspiration (cytology) of an involved site
  • Failure of doxorubicin or nitrogen mustard containing front-line therapy
  • 18F-fluorodeoxyglucose-PET scan demonstrating PET avid disease
  • Cardiac ejection fraction of greater than 45%, measured since last chemotherapy.
  • Adjusted diffusing capacity of greater than 50% on pulmonary function testing, measured since last chemotherapy
  • Serum creatinine < than or = to 1.5 mg/dl; if creatinine >1.5 mg/dl then the measured 12- or 24-hour creatinine clearance must be >60 ml/minute.
  • ANC>1000/μl and Platelets>50,000/μl
  • Total bilirubin < than or = to 2.0 mg/dl in the absence of a history of Gilbert's disease.
  • Females of childbearing age must be on an acceptable form of birth control.
  • Age between 18 and 72
  • HIV I and II negative.
  • Patients or their guardians must be capable of providing informed consent.

Exclusion Criteria:

Histology for Lymphocyte predominant subtype Hodgkin's Lymphoma

  • Prior treatment with carboplatin, cisplatin, ifosfamide, gemcitabine, or vinorelbine
  • Hepatitis B surface antigen positive.
  • Known pregnancy or breast-feeding.
  • Medical illness unrelated to Hodgkin's Lymphoma, which, in the opinion of the attending physician and/or principal investigator, will preclude administering chemotherapy safely.
  • History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cytoreductive chemotherapy group 1
Patients receive ICE comprising ifosfamide IV and carboplatin IV once on day 2 and etoposide IV over 1 hour once daily on days 1-3. Patients then receive ifosfamide IV twice on day 15, carboplatin IV once on day 17 and etoposide IV over 1 hour twice daily on days 15-17.
Drug: etoposide
Given IV
Drug: carboplatin
Given IV
Drug: ifosfamide
Given IV
EXPERIMENTAL: Cytoreductive chemotherapy group 2
Patients receive ifosfamide IV twice on days 1 and 17, carboplatin IV once on days 3 and 19, and etoposide IV over 1 hour twice daily on days 1-3 and 17-19.
Drug: etoposide
Given IV
Drug: carboplatin
Given IV
Drug: ifosfamide
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Objective Response
Time Frame: 3 years

Overall objective response to therapy Complete remission/unconfirmed (CRu)

This includes patients who meet criteria for CR with the following exceptions:

1. A residual lymph node mass > 1.5 cm in the short axis with normalization of 18Ffluorodeoxyglucose- PET scan Partial remission/minimal response (PR and MR)

  1. Any decrease in lymph nodes and nodal-based masses
  2. Any decrease in PET avidity (however, residual FDG uptake is present)
  3. Involving organs involved prior to therapy must have diminished in size.
  4. No new sites of disease Stable disease Response is less than that which constitutes a PR and disease does not meet criteria for progressive disease Progressive disease

1. Increase in lymph nodes or nodal-based masses, or other measurable disease from pretreatment observations. 2. Appearance of any new lesion at the end of therapy
3 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)

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

April 1, 2004

Primary Completion (ACTUAL)

July 1, 2012

Study Completion (ACTUAL)

July 1, 2012

Study Registration Dates

First Submitted

November 18, 2005

First Submitted That Met QC Criteria

November 18, 2005

First Posted (ESTIMATE)

November 21, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

February 1, 2016

Last Update Submitted That Met QC Criteria

December 22, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04-047
  • MSKCC-04047

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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