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

Sponsors and Collaborators:	Barbara Ann Karmanos Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00244946

Purpose

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.

Condition	Intervention	Phase
Lymphoma	Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Drug: therapeutic autologous lymphocytes Procedure: peripheral blood stem cell transplantation	Phase I

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cytarabine Cytarabine hydrochloride Etoposide Carmustine Melphalan Rituximab Etoposide phosphate Immunoglobulins Globulin, Immune Melphalan hydrochloride Sarcolysin Visilizumab Muromonab CD3

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Immune Consolidation With Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphomas

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	24
Study Start Date:	March 2004
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	15 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244946

Locations

United States, Michigan
Barbara Ann Karmanos Cancer Institute	Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute 313-576-9363
Sinai-Grace Hospital	Recruiting
Detroit, Michigan, United States, 48235
Contact: Lawrence Lum 313-576-8326

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Lawrence G. Lum, MD, DSc

Barbara Ann Karmanos Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000446079, WSU-2007-023, RWMC-0639446
Study First Received:	October 25, 2005
Last Updated:	December 4, 2008
ClinicalTrials.gov Identifier:	NCT00244946
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

nodal marginal zone B-cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma

stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma

Study placed in the following topic categories:

Melphalan
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Etoposide phosphate
Lymphoma, large-cell, immunoblastic
Muromonab-CD3
Antibodies, Bispecific
Lymphoma, B-Cell
Lymphoma, large-cell
Burkitt's lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Etoposide

Lymphoma
Cytarabine
Immunoglobulins
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Carmustine
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Antibodies
Burkitt Lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Physiological Effects of Drugs
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009