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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


Phase 1
15 Years
70 Years
Open (Enrolling)
Both
Lymphoma

Thank you

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 InstituteDetroit, Michigan  48201
Sinai-Grace HospitalDetroit, Michigan  48235