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Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

Primary Purpose

Graft Versus Host Disease, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
carmustine
melphalan
etoposide
cytarabine
tacrolimus
methotrexate
sargramostim
transplant
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring graft versus host disease, stage I mantle cell lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma

Eligibility Criteria

undefined - 59 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Documentation of Disease Histologically documented mantle cell lymphoma of any stage (needle or core biopsy is not acceptable as the sole means of diagnosis) with at least one of the following confirmatory tests indicative of diagnosis: Immunophenotype with expression of CD5 and CD19 and absence of CD23 Cytogenetic analysis with presence of t(11;14) Overexpression of cyclin D1 Rearrangement of BCL1 gene Rebiopsy of a node at relapse is recommended but not required. Bone marrow biopsy required for pretreatment evaluation. Bilateral biopsies are not required. Identification of HLA-Matched sibling donor - The sibling donor must meet eligibility criteria outlined in section 5.0 Prior Therapy Patients who have failed initial therapy are eligible (without any of the poor prognostic characteristics listed in the protocol). Failure to initial treatment is defined as one of the following: Failure to achieve clinical complete remission after treatment with an anthracycline-containing regimen Disease recurrence after initial treatment (with an anthracycline-containing regimen) Patients in first remission must have one of the following poor prognostic characteristics: International Prognostic Index (IPI) score > 1. IPI risk factors include the following: age > 60 (not eligible for this protocol); performance status > 1; LDH > normal; presence of > 1 extranodal sites; and stage III/IV disease Blastic variant of mantle cell lymphoma (regardless of IPI score) Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14) (regardless of IPI score) Proliferative index > 10% (regardless of IPI score) Presence of p53 mutations Patients who have received more than two chemotherapy regimens are ineligible. Patients who have undergone a prior bone marrow transplant are not eligible. Age < 60 years No active CNS lymphoma DLCO ≥ 40% and no symptomatic pulmonary disease No HIV infection Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control. Initial required laboratory values bilirubin < 2 mg/dl AST ≤ 3 x upper limit of normal (ULN) ALT ≤ 3 x ULN serum creatinine < 2 mg/dl u-HCG or serum HCG negative (if patient of childbearing potential)

Sites / Locations

  • Veterans Affairs Medical Center - Birmingham
  • University of California San Diego Cancer Center
  • Veterans Affairs Medical Center - San Francisco
  • UCSF Cancer Center and Cancer Research Institute
  • CCOP - Christiana Care Health Services
  • Lombardi Cancer Center
  • Walter Reed Army Medical Center
  • CCOP - Mount Sinai Medical Center
  • University of Illinois at Chicago
  • Veterans Affairs Medical Center - Chicago (Westside Hospital)
  • University of Chicago Cancer Research Center
  • Holden Comprehensive Cancer Center
  • Veterans Affairs Medical Center - Togus
  • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
  • Dana-Farber Cancer Institute
  • University of Massachusetts Memorial Medical Center - University Campus
  • Veterans Affairs Medical Center - Minneapolis
  • University of Minnesota Cancer Center
  • Veterans Affairs Medical Center - Columbia (Truman Memorial)
  • Ellis Fischel Cancer Center - Columbia
  • Barnes-Jewish Hospital
  • University of Nebraska Medical Center
  • CCOP - Southern Nevada Cancer Research Foundation
  • Norris Cotton Cancer Center
  • Veterans Affairs Medical Center - Buffalo
  • Roswell Park Cancer Institute
  • CCOP - North Shore University Hospital
  • North Shore University Hospital
  • Memorial Sloan-Kettering Cancer Center
  • New York Presbyterian Hospital - Cornell Campus
  • Mount Sinai Medical Center, NY
  • State University of New York - Upstate Medical University
  • Veterans Affairs Medical Center - Syracuse
  • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • Lineberger Comprehensive Cancer Center, UNC
  • Veterans Affairs Medical Center - Durham
  • Duke Comprehensive Cancer Center
  • CCOP - Southeast Cancer Control Consortium
  • Comprehensive Cancer Center at Wake Forest University
  • Arthur G. James Cancer Hospital - Ohio State University
  • Rhode Island Hospital
  • University of Tennessee Cancer Institute
  • Veterans Affairs Medical Center - Memphis
  • Green Mountain Oncology Group
  • Vermont Cancer Center
  • Veterans Affairs Medical Center - White River Junction
  • Veterans Affairs Medical Center - Richmond
  • MBCCOP - Massey Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

chemotherapy + stem cell transplantation

Arm Description

Patients receive carmustine, etoposide, cytarabine and melphalan on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus on day -2 and then orally twice daily until day 120 and methotrexate on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim daily beginning on day 7 and continuing until blood counts recover. Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists. Patients are followed at 6 and 12 months post-transplantation and then annually for 4 years.

Outcomes

Primary Outcome Measures

disease free survival

Secondary Outcome Measures

Full Information

First Posted
December 6, 2000
Last Updated
July 15, 2016
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006747
Brief Title
Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
Official Title
Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
November 2000 (undefined)
Primary Completion Date
February 2003 (Actual)
Study Completion Date
February 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.
Detailed Description
OBJECTIVES: Determine the long term disease-free survival of patients with mantle cell lymphoma treated with etoposide, carmustine, melphalan, and cytarabine followed by allogeneic peripheral blood stem cell transplantation. Determine the incidence of molecular remissions in these patients treated with this regimen. Correlate the persistence of minimal residual disease with clinical outcome in these patients treated with this regimen. Determine the effect of donor lymphocytes in patients with progressive disease after treatment with this regimen. OUTLINE: This is a multicenter study. Patients receive carmustine IV over 2 hours on day -6; etoposide IV over 3 hours and cytarabine IV over 1 hour every 12 hours on days -5 to -2 for a total of 8 doses; and melphalan IV over 20-30 minutes on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus IV continuously over 24 hours beginning on day -2 and then orally twice daily until day 120 and methotrexate IV over 30 minutes on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim (GM-CSF) IV or subcutaneously daily beginning on day 7 and continuing until blood counts recover. Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists. Patients are followed at 6 and 12 months posttransplantation and then annually for 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Lymphoma
Keywords
graft versus host disease, stage I mantle cell lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
chemotherapy + stem cell transplantation
Arm Type
Experimental
Arm Description
Patients receive carmustine, etoposide, cytarabine and melphalan on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus on day -2 and then orally twice daily until day 120 and methotrexate on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim daily beginning on day 7 and continuing until blood counts recover. Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists. Patients are followed at 6 and 12 months post-transplantation and then annually for 4 years.
Intervention Type
Drug
Intervention Name(s)
carmustine
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
sargramostim
Intervention Description
IV
Intervention Type
Procedure
Intervention Name(s)
transplant
Primary Outcome Measure Information:
Title
disease free survival
Time Frame
up to 5 years post-transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Documentation of Disease Histologically documented mantle cell lymphoma of any stage (needle or core biopsy is not acceptable as the sole means of diagnosis) with at least one of the following confirmatory tests indicative of diagnosis: Immunophenotype with expression of CD5 and CD19 and absence of CD23 Cytogenetic analysis with presence of t(11;14) Overexpression of cyclin D1 Rearrangement of BCL1 gene Rebiopsy of a node at relapse is recommended but not required. Bone marrow biopsy required for pretreatment evaluation. Bilateral biopsies are not required. Identification of HLA-Matched sibling donor - The sibling donor must meet eligibility criteria outlined in section 5.0 Prior Therapy Patients who have failed initial therapy are eligible (without any of the poor prognostic characteristics listed in the protocol). Failure to initial treatment is defined as one of the following: Failure to achieve clinical complete remission after treatment with an anthracycline-containing regimen Disease recurrence after initial treatment (with an anthracycline-containing regimen) Patients in first remission must have one of the following poor prognostic characteristics: International Prognostic Index (IPI) score > 1. IPI risk factors include the following: age > 60 (not eligible for this protocol); performance status > 1; LDH > normal; presence of > 1 extranodal sites; and stage III/IV disease Blastic variant of mantle cell lymphoma (regardless of IPI score) Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14) (regardless of IPI score) Proliferative index > 10% (regardless of IPI score) Presence of p53 mutations Patients who have received more than two chemotherapy regimens are ineligible. Patients who have undergone a prior bone marrow transplant are not eligible. Age < 60 years No active CNS lymphoma DLCO ≥ 40% and no symptomatic pulmonary disease No HIV infection Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control. Initial required laboratory values bilirubin < 2 mg/dl AST ≤ 3 x upper limit of normal (ULN) ALT ≤ 3 x ULN serum creatinine < 2 mg/dl u-HCG or serum HCG negative (if patient of childbearing potential)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Koen Van Besien, MD
Organizational Affiliation
University of Chicago
Official's Role
Study Chair
Facility Information:
Facility Name
Veterans Affairs Medical Center - Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233-1996
Country
United States
Facility Name
University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Veterans Affairs Medical Center - San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
CCOP - Christiana Care Health Services
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19899
Country
United States
Facility Name
Lombardi Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Walter Reed Army Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20307-5000
Country
United States
Facility Name
CCOP - Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Veterans Affairs Medical Center - Chicago (Westside Hospital)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Cancer Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1009
Country
United States
Facility Name
Veterans Affairs Medical Center - Togus
City
Togus
State/Province
Maine
ZIP/Postal Code
04330
Country
United States
Facility Name
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center - University Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Veterans Affairs Medical Center - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Veterans Affairs Medical Center - Columbia (Truman Memorial)
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65201
Country
United States
Facility Name
Ellis Fischel Cancer Center - Columbia
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65203
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-7680
Country
United States
Facility Name
CCOP - Southern Nevada Cancer Research Foundation
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Norris Cotton Cancer Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States
Facility Name
Veterans Affairs Medical Center - Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
CCOP - North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
New York Presbyterian Hospital - Cornell Campus
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Medical Center, NY
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Veterans Affairs Medical Center - Syracuse
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
City
Syracuse
State/Province
New York
ZIP/Postal Code
13217
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center, UNC
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
Facility Name
Veterans Affairs Medical Center - Durham
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
CCOP - Southeast Cancer Control Consortium
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27104-4241
Country
United States
Facility Name
Comprehensive Cancer Center at Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1082
Country
United States
Facility Name
Arthur G. James Cancer Hospital - Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
University of Tennessee Cancer Institute
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Veterans Affairs Medical Center - Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
Green Mountain Oncology Group
City
Bennington
State/Province
Vermont
ZIP/Postal Code
05201
Country
United States
Facility Name
Vermont Cancer Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401-3498
Country
United States
Facility Name
Veterans Affairs Medical Center - White River Junction
City
White River Junction
State/Province
Vermont
ZIP/Postal Code
05009
Country
United States
Facility Name
Veterans Affairs Medical Center - Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
MBCCOP - Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States

12. IPD Sharing Statement

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Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

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