Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Hodgkin's or Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002941
First received: November 1, 1999
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have recurrent or refractory Hodgkin's lymphoma or non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Drug: mesna
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Peripheral Blood Stem Cell Transplantation (PBSCT) After Preparative Therapy Consisting of Cyclophosphamide, BCNU, and Etoposide (CBV) for Recurrent and Primarily Refractory Hodgkin's and Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Failure-free survival rate [ Designated as safety issue: No ]
    Estimate the failure-free survival rate and persistent grade 3 toxicity rate of PBSCT in recurrent HD and NHL patients and to perform interim safety monitoring based on these endpoints.


Secondary Outcome Measures:
  • Estimating parameters relevant to recovery of normal bone marrow function [ Designated as safety issue: No ]
  • Predictive value of MRD assessment [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: April 1998
Study Completion Date: March 2007
Primary Completion Date: November 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reinduction Therapy
Two courses of reinduction chemotherapy followed by bone marrow biopsy and aspirate prior to peripheral blood stem cell (PBSC) harvest. If marrow involvement is still present at harvest, then 2 additional courses of induction chemotherapy are given. The PBSC transplantation preparative regimen should begin within 2 weeks of completing reinduction therapy course, consisting of the following: Carmustine IV over 3 hours on days -8, -7, and -6, Etoposide continuous IV over days -8, -7, and -6, Cyclophosphamide IV over 1 hour daily on days -5, -4, -3, and -2, Mesna as a 15 min infusion before each dose of cyclophosphamide then at 3, 6, 9, and 12 hours after initiation of each cyclophosphamide dose Methylprednisolone IV is given to protect lungs from the toxic effects of carmustine.
Drug: carmustine
Other Names:
  • BCNU
  • NSC-409962
Drug: cyclophosphamide
Other Names:
  • Cytoxan
  • NSC-26271
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC-141540
Drug: mesna
Other Names:
  • Mesnex
  • NSC-113891
Procedure: peripheral blood stem cell transplantation

Detailed Description:

OBJECTIVES:

  • Estimate the failure-free survival rate in a cohort of relapsed Hodgkin's lymphoma and non-Hodgkin's lymphoma patients after retrieval therapy which includes peripheral blood stem cell transplantation (PBSCT) in patients who achieve a complete remission or partial remission.
  • Estimate the post complete/partial remission failure-free survival rate in these patients.
  • Characterize the time to recovery of normal bone marrow function after transplantation in these patients.

OUTLINE: Patients receive 2 courses of reinduction chemotherapy followed by bone marrow biopsy and aspirate prior to peripheral blood stem cell (PBSC) harvest. If marrow involvement is still present at harvest, then 2 additional courses of induction chemotherapy are given.

The PBSC transplantation preparative regimen should begin within 2 weeks of completing reinduction therapy course, consisting of the following:

  • Carmustine IV over 3 hours on days -8, -7, and -6
  • Etoposide continuous IV over days -8, -7, and -6
  • Cyclophosphamide IV over 1 hour daily on days -5, -4, -3, and -2
  • Mesna as a 15 min infusion before each dose of cyclophosphamide then at 3, 6, 9, and 12 hours after initiation of each cyclophosphamide dose Methylprednisolone IV is given to protect lungs from the toxic effects of carmustine.

PROJECTED ACCRUAL: A total of 30 patients will be accrued in each subgroup.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed non-Hodgkin's lymphoma in first relapse or refractory after primary induction therapy
  • Histologically confirmed Hodgkin's lymphoma in first relapse after chemotherapy with more than one nodal region involved at relapse or refractory after primary induction therapy (i.e., failed to achieve remission at the conclusion of standard induction chemotherapy)

    • No prior radiotherapy only for low stage nodal disease
    • No greater than 4 courses of standard chemotherapy for low stage nodal disease
  • CSF or bone marrow involvement at time of study entry is allowed

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21 (at initial diagnosis)

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • SGOT or SGPT less than 2.5 times normal
  • Bilirubin no greater than 1.5 mg/dL

Renal:

  • Creatinine less than 1.5 mg/dL
  • Glomerular filtration rate greater than 60 mL/min as measured by radionuclide scan or 24 hour urine collection for creatinine clearance

Cardiovascular:

  • Shortening fraction of at least 28% by echocardiogram
  • Ejection fraction of at least 40% by radionuclide angiogram echocardiogram

Pulmonary:

  • Total lung capacity (TLC) at least 50% OR
  • Vital capacity (VC) at least 65% of normal
  • DLCO at least 55% of normal
  • For children who are uncooperative to pulmonary function testing, no dyspnea at rest or with mild exercise, and a pulse oximetry of at least 95%

Other:

  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • Not specified
  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: NCT00002941

  Show 235 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Richard E. Harris, MD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002941     History of Changes
Other Study ID Numbers: A5962, COG-A5962, CCG-A5962, POG-A5962, CCG-5962, CDR0000065390
Study First Received: November 1, 1999
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent childhood lymphoblastic lymphoma
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Carmustine
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014