Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00244946|
Recruitment Status : Completed
First Posted : October 27, 2005
Last Update Posted : March 26, 2015
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 or disease||Intervention/treatment||Phase|
|Lymphoma||Biological: therapeutic autologous lymphocytes Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: peripheral blood stem cell transplantation (PBSCT)||Phase 1|
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||March 2004|
|Actual Primary Completion Date :||January 2010|
|Actual Study Completion Date :||March 2013|
Experimental: Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
Biological: therapeutic autologous lymphocytes
Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection
Procedure: peripheral blood stem cell transplantation (PBSCT)
- 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. [ Time Frame: 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.
- Evaluate the toxicities of ATC infusions armed with CD20Bi [ Time Frame: 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 immune B-cell recovery after ATC infusion [ Time Frame: 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 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00244946
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Study Chair:||Lawrence G. Lum, MD, DSc||Barbara Ann Karmanos Cancer Institute|