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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
therapeutic autologous lymphocytes
carmustine
cytarabine
etoposide
melphalan
peripheral blood stem cell transplantation (PBSCT)
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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, 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, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma

Eligibility Criteria

15 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Evaluate the toxicities of ATC infusions armed with CD20Bi
Evaluate immune B-cell recovery after ATC infusion
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.

Full Information

First Posted
October 25, 2005
Last Updated
March 25, 2015
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00244946
Brief Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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, 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, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
therapeutic autologous lymphocytes
Intervention Description
Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection
Intervention Type
Drug
Intervention Name(s)
carmustine
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation (PBSCT)
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
When two patienst at any dose levet have their infusion stopped due to side effects.
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
Evaluate response rates of infusions and compare relapse rates and overall survival to historical controls
Description
Survival follow-up: 1 year, 3 years, 5 years and 10 years after transplant.
Time Frame
1, 2, 4, 8, 16 and/or 24, 48 and 72 hours post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence G. Lum, MD, DSc
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-1379
Country
United States

12. IPD Sharing Statement

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

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