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Autologous or Donor Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin's Lymphoma (BMT CTN 0202)

Primary Purpose

Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide and Rituximab
Filgrastim
Chemotherapy or Radiation therapy
Non-myeloablative Conditioning regimen
Allogeneic transplant
Autologous transplant
Rituximab maintenance therapy
GVHD Prophylaxis
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Grade 1 Follicular Lymphoma

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Initial Patient Inclusion Criteria: Histologically confirmed recurrent Revised European American Lymphoma (REAL) classification follicle center lymphoma, follicular grades I and II, OR histologically confirmed World Health Organization (WHO) classification follicular lymphoma grades 1, 2, 3a or 3b; for either classification, the diffuse component or presence of large cleaved cells (if present) cannot be more than 50% of high power field; patients do not have to express t(14;18) to be eligible Received three or fewer prior regimens of chemotherapy; monoclonal antibody therapy and involved field radiation therapy will not be counted as a prior therapy Beyond first Complete Remission (CR) or first Partial Remission (PR) AND demonstrate chemosensitive disease; chemosensitive disease will be defined as less than 20% bone marrow involvement in the aspirate or core biopsy with follicular lymphoma AND lymph node size in axial diameter of less than 3 cm or a greater than 50% reduction in estimated lymph node volume to be measured as product of bi-dimensional measurements; Positron Emission Tomography (PET) scanning will not be used for staging or response purposes Patients with adequate organ function as measured by: Cardiac: left ventricular ejection fraction at rest at least 45% Hepatic: bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal Renal: creatinine clearance greater than 40 mL/min Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), Forced expiratory volume in one second (FEV1), and Forced vital capacity (FVC) greater than 50% of predicted (corrected for hemoglobin) If the patient is younger than 18 years of age and they have reached the age of assent, then they must have completed the local Institutional Review Board (IRB) assent process. Able to receive cyclophosphamide and rituximab mobilization chemotherapy no earlier than 3 weeks from the beginning of the most recent cycle of salvage chemotherapy and no later than 6 weeks from enrollment Patient Inclusion Criteria for Proceeding to Hematopoietic Stem Cell Transplant (HSCT): Collection of an autologous or allogeneic graft of at least 2.0 * 10^6 CD34+ cells/kg Blood count recovery defined as Absolute Neutrophil Count (ANC) greater than 1000/mm3 and platelets greater than 100 * 10^9/L Patient Inclusion Criteria for Maintenance Therapy: Liver and renal function tests within the inclusion criteria for initial autograft Off intravenous antibiotics and off amphotericin B formulations for proven, probable or possible fungal infections No active Cytomegalovirus (CMV) infections or for patients with CMV infection post-autograft, treated with ganciclovir, valganciclovir, or foscarnet per institutional guidelines and CMV antigenemia negative Mucositis resolved and off hyperalimentation Exclusion Criteria: Karnofsky performance score less than 70% Follicular lymphoma that show histologic evidence of transformation Uncontrolled hypertension Patients with uncontrolled bacterial, viral or fungal infection (currently taking medication and progression without clinical improvement). Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent more than 5 years previously will be reviewed on a case-by-case basis by a Protocol Chair or Medical Monitor. Pregnant (positive Beta Human chorionic gonadotropin (β-HCG)) or breastfeeding Seropositive for Human immunodeficiency virus (HIV) Unwilling to use contraceptive techniques during treatment Prior autologous or allogeneic HSCT Known anaphylactic reaction to rituximab

Sites / Locations

  • City of Hope National Medical Center
  • Scripps Clinic
  • UCSD Medical Center
  • Stanford Hospital and Clinics
  • University of Florida College of Medicine (Shands)
  • H. Lee Moffitt Cancer Center
  • Emory University
  • BMT Group of Georgia
  • Loyola University
  • Indiana BMT at Beech Grove
  • Dana-Farber Cancer Institute
  • University of Michigan Medical Center
  • Karmanos Cancer Institute/BMT
  • University of Minnesota
  • Kansas City Cancer Centers
  • Washington University/Barnes Jewish Hospital
  • University of Nebraska Medical Center
  • Hackensack University Medical Center
  • Duke University Medical Center
  • University Hospitals of Cleveland/Case Western
  • Providence Portland Medical Center
  • Oregon Health Sciences University
  • University of Pennsylvania Cancer Center
  • University of Pittsburgh Cancer Institute
  • Vanderbilt University
  • Baylor University Medical Center
  • University of Texas/MD Anderson CRC
  • Virginia Commonwealth University MCV Hospitals
  • University of Wisconsin Hospital and Clinics
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Autologous Transplant

Allogeneic Transplant

Arm Description

Cyclophosphamide and Rituximab with Filgrastim conditioning and chemotherapy or radiation therapy prior to autologous Hematopoietic Stem Cell Transplant (HSCT). Rituximab maintenance therapy following HSCT.

Non-myeloablative conditioning regimen followed by allogeneic Hematopoietic Stem Cell Transplant (HSCT). Graft-versus-Host Disease (GVHD) Prophylaxis therapy following HSCT.

Outcomes

Primary Outcome Measures

Lymphoma Progression-free Survival

Secondary Outcome Measures

Full Information

First Posted
November 9, 2004
Last Updated
December 7, 2022
Sponsor
Medical College of Wisconsin
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program
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1. Study Identification

Unique Protocol Identification Number
NCT00096460
Brief Title
Autologous or Donor Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin's Lymphoma (BMT CTN 0202)
Official Title
Autologous Versus Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Chemosensitive Follicular Non-Hodgkin's Lymphoma Beyond First Complete Response or First Partial Response (BMT CTN #0202)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
lower than anticipated accrual
Study Start Date
August 2004 (undefined)
Primary Completion Date
March 2006 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical College of Wisconsin
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed as a Phase II/III, multi-center trial, comparing two transplant strategies to determine whether non-myeloablative allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will improve long-term progression-free survival compared to autologous HSCT. Recipients will be biologically assigned to the appropriate treatment arm depending on the availability of a Human Leukocyte Antigen (HLA) matched sibling.
Detailed Description
BACKGROUND: Although patients with follicular non-Hodgkin's lymphoma (NHL) typically experience a relatively indolent course, the disease is rarely curable with conventional chemotherapy. Patients with follicular NHL are usually treated only when symptoms require palliation or if bulky disease exists since no survival advantage has been shown as compared to administering conventional treatment at initial diagnosis. While most patients achieve a remission with initial chemotherapy, a continuous pattern of relapse occurs, resulting in progressively shorter remission durations. Additionally, the increased response rates conferred by anthracycline-containing regimens have not translated into improved survival and thus the median survival time of 6 to 10 years has not been significantly impacted over the last decade. DESIGN NARRATIVE: The overall study design is a comparison of two treatment arms determined by biologic assignment, based on the availability of an HLA-matched sibling, in patients diagnosed with relapsed follicular non-Hodgkin's lymphoma. Patients without an HLA-matched sibling will receive an autologous HSCT. Patients with an HLA-matched sibling will receive a non-myeloablative allogeneic HSCT. The overall study design is that of biologic assignment, based on the availability of an HLA-matched sibling, to one of two strategies to improve the outcome for follicular lymphoma patients with chemosensitive disease. All patients will undergo cytoreduction with cyclophosphamide 4 gm/m^2 and rituximab 375 mg/m^2 x 2 doses. Rituximab will be given in two doses, approximately 1 week apart, with the cyclophosphamide administered the day after the first dose of rituximab. Patients assigned to the autologous arm will have their hematopoietic stem cells mobilized from this cytoreductive regimen. Patients with an HLA-matched sibling will undergo a non-myeloablative allogeneic HSCT. Pre-transplant conditioning will consist of fludarabine 30 mg/m^2/day and cyclophosphamide 750 mg/m^2/day x 3 days with rituximab 375 mg/m^2/day on Days -13 and -6 pre-HSCT and on Days +1 and +8 post-HSCT. The immunosuppressive regimen will consist of tacrolimus and methotrexate (MTX) to control graft-versus-host and host-versus-graft reactions. Patients without an HLA-matched sibling who have collected an adequate autologous hematopoietic cell graft, defined as at least 2.0 * 10^6 CD34+ cells/kg, will receive a preparative regimen of total body irradiation (TBI) 1200 cGy or Carmustine (BCNU) 15 mg/kg. In addition, VP-16 60 mg/kg and cyclophosphamide 100 mg/kg will be given for both autologous preparative regimens. Post-autologous HSCT therapy with rituximab 375 mg/m^2 weekly x 4 doses will commence between Days 42-75 post-HSCT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Follicular Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Autologous Transplant
Arm Type
Active Comparator
Arm Description
Cyclophosphamide and Rituximab with Filgrastim conditioning and chemotherapy or radiation therapy prior to autologous Hematopoietic Stem Cell Transplant (HSCT). Rituximab maintenance therapy following HSCT.
Arm Title
Allogeneic Transplant
Arm Type
Active Comparator
Arm Description
Non-myeloablative conditioning regimen followed by allogeneic Hematopoietic Stem Cell Transplant (HSCT). Graft-versus-Host Disease (GVHD) Prophylaxis therapy following HSCT.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide and Rituximab
Other Intervention Name(s)
Cytoxan® and Rituxan
Intervention Description
Prior to undergoing HSCT, all patients will receive Cyclophosphamide 4 gm/m2 with Rituximab 375 mg/m2 x 2 doses and G-CSF support.
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
Autologous HSCT patients will receive 10 mcg/kg/day and allogeneic HSCT patients will receive 5 mcg/kg/day subcutaneous (SQ) or intravenous (IV) starting 2 days after the initiation of Cyclophosphamide.
Intervention Type
Radiation
Intervention Name(s)
Chemotherapy or Radiation therapy
Other Intervention Name(s)
Etoposide and Carmustine, BCNU and VP-16
Intervention Description
Chemotherapy - BCNU 15 mg/kg IV x 1 dose to be administered over 2 hours on Day -6 pre-HSCT. VP-16 60 mg/kg IV x 1 dose to be administered over 4 hours on Day -4. Radiation - administered at a rate of < 20 cGy/min in one of the following doses; 120 cGy/fraction are administered at no less than 4-hour intervals three times/day or 2 times/day for a total of 10 doses (1200 cGy) over 4 days (Day -8, -7, -6 and -5), or doses of 150 cGy/fraction twice daily for a total of 8 doses (1200 cGy) over 4 days (Day -8, -7, -6 and -5). VP-16 60 mg/kg IV x 1 dose to be administered over 4 hours on Day -4 pre-HSCT. Cyclophosphamide 100 mg/kg IV x 1 dose to be administered over 2 hours on Day -2 pre-HSCT. G-CSF 5 mcg/kg SQ or IV to start on Day +5 post-HSCT and continue until ANC > 500/mm3 x 3 days.
Intervention Type
Drug
Intervention Name(s)
Non-myeloablative Conditioning regimen
Other Intervention Name(s)
Fludarabine, Cyclophosphamide, and Rituximab, Fludara, Cytoxan®, and Rituxan
Intervention Description
Fludarabine 30 mg/m2 IV x 3 doses total to be administered daily over 30 minutes on Days -6, -5 and -4 pre-HSCT. Cyclophosphamide 750 mg/m IV x 3 doses total to be administered daily over 1 hour on Days -6, -5 and -4 pre-HSCT. Administer cyclophosphamide approximately 4 hours after start of fludarabine infusion. Rituximab 375 mg/m2 IV x 4 doses total to be administered on Days -13 and -6 pre HSCT and Days +1 and +8 post HSCT.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic transplant
Other Intervention Name(s)
HSCT
Intervention Description
Infusion of G-CSF mobilized allogeneic hematopoietic stem cells
Intervention Type
Procedure
Intervention Name(s)
Autologous transplant
Other Intervention Name(s)
HSCT
Intervention Description
Infusion of G-CSF mobilized autologous hematopoietic stem cells
Intervention Type
Drug
Intervention Name(s)
Rituximab maintenance therapy
Other Intervention Name(s)
Rituxan
Intervention Description
Patients must have sufficiently recovered from autologous HSCT in order to receive rituximab maintenance therapy as specified below: Dose #1: Day +42 post-autologous HSCT Dose #2: Day +49 post-autologous HSCT Dose #3: Day +56 post-autologous HSCT Dose #4: Day +63 post-autologous HSCT
Intervention Type
Drug
Intervention Name(s)
GVHD Prophylaxis
Other Intervention Name(s)
Tacrolimus and Methotrexate, Prograf® and MTX
Intervention Description
Tacrolimus 0.09 mg/kg/day PO, based on body weight formulas will start on Day -2 and continue until Day +90 post-HSCT. Tacrolimus (or cyclosporine, if applicable) will be given orally in a twice-daily divided dose. Methotrexate 5 mg/m2 Intravenous Pyelogram (IVP) will be administered on Days +1, +3 and +6 post-HSCT.
Primary Outcome Measure Information:
Title
Lymphoma Progression-free Survival
Time Frame
Three years post-Hematopoietic Stem Cell Transplant (HSCT)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Initial Patient Inclusion Criteria: Histologically confirmed recurrent Revised European American Lymphoma (REAL) classification follicle center lymphoma, follicular grades I and II, OR histologically confirmed World Health Organization (WHO) classification follicular lymphoma grades 1, 2, 3a or 3b; for either classification, the diffuse component or presence of large cleaved cells (if present) cannot be more than 50% of high power field; patients do not have to express t(14;18) to be eligible Received three or fewer prior regimens of chemotherapy; monoclonal antibody therapy and involved field radiation therapy will not be counted as a prior therapy Beyond first Complete Remission (CR) or first Partial Remission (PR) AND demonstrate chemosensitive disease; chemosensitive disease will be defined as less than 20% bone marrow involvement in the aspirate or core biopsy with follicular lymphoma AND lymph node size in axial diameter of less than 3 cm or a greater than 50% reduction in estimated lymph node volume to be measured as product of bi-dimensional measurements; Positron Emission Tomography (PET) scanning will not be used for staging or response purposes Patients with adequate organ function as measured by: Cardiac: left ventricular ejection fraction at rest at least 45% Hepatic: bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal Renal: creatinine clearance greater than 40 mL/min Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), Forced expiratory volume in one second (FEV1), and Forced vital capacity (FVC) greater than 50% of predicted (corrected for hemoglobin) If the patient is younger than 18 years of age and they have reached the age of assent, then they must have completed the local Institutional Review Board (IRB) assent process. Able to receive cyclophosphamide and rituximab mobilization chemotherapy no earlier than 3 weeks from the beginning of the most recent cycle of salvage chemotherapy and no later than 6 weeks from enrollment Patient Inclusion Criteria for Proceeding to Hematopoietic Stem Cell Transplant (HSCT): Collection of an autologous or allogeneic graft of at least 2.0 * 10^6 CD34+ cells/kg Blood count recovery defined as Absolute Neutrophil Count (ANC) greater than 1000/mm3 and platelets greater than 100 * 10^9/L Patient Inclusion Criteria for Maintenance Therapy: Liver and renal function tests within the inclusion criteria for initial autograft Off intravenous antibiotics and off amphotericin B formulations for proven, probable or possible fungal infections No active Cytomegalovirus (CMV) infections or for patients with CMV infection post-autograft, treated with ganciclovir, valganciclovir, or foscarnet per institutional guidelines and CMV antigenemia negative Mucositis resolved and off hyperalimentation Exclusion Criteria: Karnofsky performance score less than 70% Follicular lymphoma that show histologic evidence of transformation Uncontrolled hypertension Patients with uncontrolled bacterial, viral or fungal infection (currently taking medication and progression without clinical improvement). Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent more than 5 years previously will be reviewed on a case-by-case basis by a Protocol Chair or Medical Monitor. Pregnant (positive Beta Human chorionic gonadotropin (β-HCG)) or breastfeeding Seropositive for Human immunodeficiency virus (HIV) Unwilling to use contraceptive techniques during treatment Prior autologous or allogeneic HSCT Known anaphylactic reaction to rituximab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Horowitz, MD
Organizational Affiliation
Center for International Blood and Marrow Transplant Research
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCSD Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Florida College of Medicine (Shands)
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0277
Country
United States
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33624
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
BMT Group of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Loyola University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana BMT at Beech Grove
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
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 Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105-2967
Country
United States
Facility Name
Karmanos Cancer Institute/BMT
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Kansas City Cancer Centers
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Washington University/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
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University Hospitals of Cleveland/Case Western
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5061
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
Facility Name
University of Pennsylvania Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-8210
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas/MD Anderson CRC
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Commonwealth University MCV Hospitals
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-5156
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53211
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
21073974
Citation
Tomblyn MR, Ewell M, Bredeson C, Kahl BS, Goodman SA, Horowitz MM, Vose JM, Negrin RS, Laport GG. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response. Biol Blood Marrow Transplant. 2011 Jul;17(7):1051-7. doi: 10.1016/j.bbmt.2010.11.004. Epub 2010 Nov 10.
Results Reference
result
Links:
URL
https://bethematch.org/
Description
National Marrow Donor Program

Learn more about this trial

Autologous or Donor Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin's Lymphoma (BMT CTN 0202)

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