Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma

NCT ID: NCT00244946

Last Updated: 2015-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2013-03-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan 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. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving white blood cells, that have been treated in the laboratory with antibodies, may make the transplant work better. Giving combination chemotherapy followed by an autologous stem cell transplant, and white blood cell infusions may be an effective treatment for non-Hodgkin's lymphoma.

PURPOSE: This phase I trial is studying the side effects and best dose of white blood cell infusions when given together with combination chemotherapy, and autologous stem cell transplant in treating patients with non-Hodgkin's lymphoma that has relapsed, is refractory, or is in remission.

Detailed Description

OBJECTIVES:

• Determine the toxicity of high-dose combination chemotherapy comprising cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with non-Hodgkin's lymphoma.
• Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this regimen.
• Determine whether ATC traffic to tumor sites in select patients treated with this regimen.
• Assess the immune reconstitution of B cells and incidence of infection in patients treated with this regimen.
• Compare relapse rates and overall survival of patients treated with this regimen with historical controls.

OUTLINE: This is a dose-escalation study of activated T cells.

• Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes are treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC).
• High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day -7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3, and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.
• Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total of four infusions.

Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

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

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT

• minus Day 8 ADMIT for Hydration
• minus Day 7 Carmustine 300 mg/m2 x 1 dose
• minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
• minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
• minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
• minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
• minus Day 2 Melphalan 140 mg/m2 x 1 dose
• minus Day 1 Day of Rest
• Day 0 Transplant

Group Type: EXPERIMENTAL

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection

carmustine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

peripheral blood stem cell transplantation (PBSCT)

Intervention Type: PROCEDURE

Interventions

therapeutic autologous lymphocytes

Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

peripheral blood stem cell transplantation (PBSCT)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed CD20+ non-Hodgkin's lymphoma

• Disease is refractory, relapsed, or in remission
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin > 8 g/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 50,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• SGOT or SGPT ≤ 2.5 times normal
• No history of severe hepatic dysfunction

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• No uncompensated major adrenal dysfunction
• BUN < 1.5 times normal

Cardiovascular

• No severe cardiac dysfunction
• No major heart disease
• LVEF ≥ 50% by MUGA
• No uncontrolled hypertension
• No congenital or acquired heart disease or cardiac arrhythmias unless cardiac consult and evaluation are done

Pulmonary

• DLCO ≥ 50% of normal
• No symptomatic obstructive or restrictive disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infections
• HIV negative
• No significant skin breakdown from tumor or other diseases
• Dental evaluation and teeth cleaning with no potential sources of infection required
• No uncompensated major thyroid dysfunction

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior stem cell transplantation

Chemotherapy

• No prior total doxorubicin or daunorubicin dose ≥ 450 mg/m^2 unless endomyocardial biopsy shows < grade 2 drug effect AND ejection fraction ≥ 50% by gated blood pool scan

Endocrine therapy

• No concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for diabetes)

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Lawrence Lum

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lawrence G. Lum, MD, DSc

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-2007-023

Identifier Type: -

Identifier Source: secondary_id

RWMC-0639446

Identifier Type: -

Identifier Source: secondary_id

CDR0000446079

Identifier Type: -

Identifier Source: org_study_id