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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244946
• Other study ID #: CDR0000446079
• Secondary ID: P30CA022453WSU-2
• Status: Completed
• Phase: Phase 1
• First received: October 25, 2005
• Last updated: March 25, 2015
• Start date: March 2004
• Est. completion date: March 2013

Study information

• Verified date: March 2015
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2013
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 70 Years

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• therapeutic autologous lymphocytes
Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection

Drug:
• carmustine

• cytarabine

• etoposide

• melphalan

Procedure:
• peripheral blood stem cell transplantation (PBSCT)

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To perform a dose escalation trial of ATC armed with CD20Bi immunotherapy after PBSCT to determine the maximum tolerated dose (MTD) of ATC armed with CD20BI.	This will be the called the maximum tolerated dose. The maximum tolerated dose (MTD) is defined as the dose level below the one at which the side effects are serious enough to prevent an increase in the dose or level of the treatment.	When two patienst at any dose levet have their infusion stopped due to side effects.	Yes
Secondary	Evaluate the toxicities of ATC infusions armed with CD20Bi		2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT)	Yes
Secondary	Evaluate immune B-cell recovery after ATC infusion		2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT)	Yes
Secondary	Evaluate response rates of infusions and compare relapse rates and overall survival to historical controls	Survival follow-up: 1 year, 3 years, 5 years and 10 years after transplant.	1, 2, 4, 8, 16 and/or 24, 48 and 72 hours post infusion	No