Peripheral Stem Cell Transplantation to Prevent Neutropenia in Patients Receiving Chemotherapy for Relapsed or Refractory Non-Hodgkin's Lymphoma

Northwestern University

Status and phase: Terminated; Phase 1

Conditions: Neutropenia; Lymphoma

Treatments: Biological: recombinant interleukin-3; Biological: sargramostim; Biological: recombinant flt3 ligand; Biological: epoetin alfa; Procedure: in vitro-treated peripheral blood stem cell transplantation; Biological: filgrastim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005787

NU 99Z1

NU-99Z1

NCI-G00-1734

Details and patient eligibility

About

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Treating the peripheral stem cells in the laboratory may improve the effectiveness of the transplant.

PURPOSE: Phase I trial to study the effectiveness of peripheral stem cell transplantation in patients who have relapsed or refractory non-Hodgkin's lymphoma and who will be treated with high-dose chemotherapy.

Full description

OBJECTIVES:

• Determine the toxicity of ex vivo expanded peripheral blood mononuclear cells (EVE PBMNC) as a supplement to high-dose chemotherapy and conventional autograft in patients with relapsed or refractory non-Hodgkin's lymphoma.
• Compare the effect of EVE PBMNC on white blood cell, red blood cell, and platelet recovery in patients on this study vs historical controls, matched by protocol, disease status, and prior therapy.
• Determine the optimal duration of culture and time of harvest for the production of neutrophils in vivo.
• Determine the relationships between length of culture, immunophenotype, and clinical outcome.
• Determine the required numbers of white blood cell precursors for clinical efficacy.
• Assess the need for multiple transfusions of EVE PBMNC during the post-transplantation period.

OUTLINE: Autologous peripheral blood mononuclear cells (PBMNC) are harvested. Unselected PBMNC are cultured and expanded ex vivo in flt3 ligand, interleukin-3, filgrastim (G-CSF), sargramostim (GM-CSF), and epoetin alfa for 13 days. Expanded PBMNC are reinfused on day 0.

Patients are followed monthly for 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Enrollment: 3 patients

Sex: All

Ages: 17 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven relapsed or refractory non-Hodgkin's lymphoma
• Scheduled to undergo high-dose chemotherapy (carmustine, etoposide, cytarabine, and melphalan) with autologous peripheral blood mononuclear cell transplantation
• No metastatic disease involving the bone marrow

PATIENT CHARACTERISTICS:

Age:

• 17 to 65

Performance status:

• ECOG 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• No active hepatitis B or C
• Bilirubin less than 2.5 times normal*
• SGOT or SGPT less than 2.5 times normal*
• Alkaline phosphatase less than 2.5 times normal NOTE: * Unless Gilbert's syndrome present

Renal:

• Creatinine clearance greater than 50 mL/min

Cardiovascular:

• Cardiac ejection fraction normal

Pulmonary:

• DLCO at least 50% predicted
• FEV_1 and FVC at least 75% predicted

Other:

• HIV negative
• Not pregnant
• Negative pregnancy test
• No non-neoplastic disease that would preclude intensive chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior external beam radiotherapy to more than 25% of the active bone marrow

Surgery:

• Not specified