Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma
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
Acronym
Not provided
Organization
Barbara Ann Karmanos Cancer InstituteOTHER
Status Module
Record Verification Date
Mar 2015
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 2004
Primary Completion Date
Jan 2010Actual
Completion Date
Mar 2013Actual
First Submitted Date
Oct 25, 2005
First Submission Date that Met QC Criteria
Oct 25, 2005
First Posted Date
Oct 27, 2005Estimated
Results Waived
Not provided
Results First Submitted Date
Not provided
Results First Submitted that Met QC Criteria
Not provided
Results First Posted Date
Not provided
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 25, 2015
Last Update Posted Date
Mar 26, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Lawrence Lum, Principal Investigator, Barbara Ann Karmanos Cancer InstitutePrincipal Investigator
Lead Sponsor
Barbara Ann Karmanos Cancer InstituteOTHER
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Lymphoma
Keywords
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
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.
Secondary Outcomes
Measure
Description
Time Frame
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)
Evaluate immune B-cell recovery after ATC infusion
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)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
15 Years
Maximum Age
70 Years
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Lawrence G. Lum, MD, DSc
Barbara Ann Karmanos Cancer Institute
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
48201-1379
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
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No data is available for this block.
Results Section
No data available
No data is available for this block.
Annotation Section
No data available
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Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
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