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

Phase 1

Completed

• Conditions: Lymphoma
• Interventions: Biological: therapeutic autologous lymphocytes; Drug: carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation (PBSCT)

• Registration Number: NCT00244946
• Lead Sponsor: Barbara Ann Karmanos Cancer Institute

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.

Study Timeline

• Study Start: 2004-03
• Study First Submitted: 2005-10-25
• Study First Submitted QC: 2005-10-25
• Study First Posted: 2005-10-27
• Primary Completion: 2010-01
• Study Completion: 2013-03
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-25
• Last Update Posted: 2015-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	cytarabine	* 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
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	therapeutic autologous lymphocytes	* 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
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	peripheral blood stem cell transplantation (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
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	carmustine	* 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
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	etoposide	* 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
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT	melphalan	* 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

Primary Outcome Measures

Name	Time	Method
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.	When two patienst at any dose levet have their infusion stopped due to side effects.	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.

Secondary Outcome Measures

Name	Time	Method
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)
Evaluate response rates of infusions and compare relapse rates and overall survival to historical controls	1, 2, 4, 8, 16 and/or 24, 48 and 72 hours post infusion	Survival follow-up: 1 year, 3 years, 5 years and 10 years after transplant.
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)

Trial Locations

Locations (1)

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States