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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00255723
First received: November 18, 2005
Last updated: August 22, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: carboplatin
Drug: etoposide
Drug: ifosfamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Adapted High Dose Chemoradiotherapy and Autologous Stem Cell Transplantation for Patients With Relapsed and Primary Refractory Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Event-free survival at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 98
Study Start Date: April 2004
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: carboplatin
Given IV
Drug: etoposide
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: carboplatin
Given IV
Drug: etoposide
Given IV
Drug: ifosfamide
Given IV

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00255723

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Craig Moskowitz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00255723     History of Changes
Other Study ID Numbers: 04-047, MSKCC-04047
Study First Received: November 18, 2005
Last Updated: August 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
adult lymphocyte depletion Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Isophosphamide mustard
Etoposide phosphate
Carboplatin
Ifosfamide
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014