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
15 Years
70 Years
Both
Lymphoma
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Lawrence G. Lum, MD, DSc
Investigator Role:
Study Chair
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000446079
NCT ID:
NCT00244946
Start Date:
March 2004
Completion Date:
Related Keywords:
- Lymphoma
- 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
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| Sinai-Grace Hospital | Detroit, Michigan 48235 |
