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

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Procedure: peripheral blood stem cell transplantation; Drug: carmustine; Drug: mesna; Drug: etoposide; Drug: cyclophosphamide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00002941

CDR0000065390 (Other Identifier)

COG-A5962 (Other Identifier)

CCG-A5962 (Other Identifier)

POG-A5962 (Other Identifier)

CCG-5962 (Other Identifier)

A5962

Details and patient eligibility

About

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.

Full 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.

Enrollment: 69 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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69 participants in 1 patient group

Reinduction Therapy

Experimental group

Description:

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.

Treatment:

Procedure: peripheral blood stem cell transplantation

Drug: etoposide

Drug: cyclophosphamide

Drug: mesna

Drug: carmustine