COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Lawrence Lum, Barbara Ann Karmanos Cancer Institute

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


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

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Carmustine

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Autologous lymphocytes,carmustine,etoposide, melphalan, 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
 Biological: therapeutic autologous lymphocytes
Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection

Drug: carmustine
Drug: cytarabine
Drug: etoposide
Drug: melphalan
Procedure: peripheral blood stem cell transplantation (PBSCT)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Lawrence G. Lum, MD, DSc Barbara Ann Karmanos Cancer Institute
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Lawrence Lum, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00244946    
Other Study ID Numbers: CDR0000446079
P30CA022453 ( U.S. NIH Grant/Contract )
WSU-2007-023
RWMC-0639446
First Posted: October 27, 2005    Key Record Dates
Last Update Posted: March 26, 2015
Last Verified: March 2015
Keywords provided by Lawrence Lum, Barbara Ann Karmanos Cancer Institute:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Etoposide
Melphalan
Carmustine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
 Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists