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Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Extracorporeal Photopheresis
Pentostatin
Total body irradiation (TBI)
Allogeneic bone marrow transplantation
Cyclosporin (CSA)
Mycophenolate mofetil (MMF)
Methotrexate (MTX)
Sponsored by
Eastern Cooperative Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt 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 mycosis fungoides/Sezary syndrome, recurrent adult T-cell leukemia/lymphoma, anaplastic large cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

Eligibility Criteria

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

Inclusion Criteria: Non-Hodgkin's or Hodgkin's lymphoma that has relapsed following either a course of high dose chemotherapy or autologous stem cell transplantation. >= 90 days from prior transplant. Have a suitable human leukocyte antigen (HLA)-matched related bone marrow donor or a compatible matched unrelated bone marrow donor by molecular typing at HLA A, B, C, D, DR. Physically and psychologically capable of undergoing bone marrow transplantation and its attendant period of strict isolation. Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Be able to receive 400 cGy Total Body Irradiation (TBI). Pulmonary function tests: Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO) >= 50% predicted, the forced expiratory volume in 1 second (FEV1) >= 50% predicted. Left ventricular ejection fraction (LVEF) at least 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram. Renal function: creatinine clearance > 50 ml/min. Liver function tests: < 3 x Upper Limit of Normal (ULN). Liver function test include serum glutamic oxaloacetic transaminase (SGOT) (Aspartate transaminase (AST)), Serum Glutamic Pyruvate Transaminase (SGPT) (Alanine transaminase (ALT)), and bilirubin. Exclusion Criteria: Human immunodeficiency virus positive (HIV+) patients (test positive for P21 antibodies to HIV). Evidence of active infection (have received parenteral antibiotics <= 2 weeks prior to registration). Pregnant or breast-feeding women. Curable with any other therapeutic interventions.

Sites / Locations

  • Aurora Presbyterian Hospital
  • Boulder Community Hospital
  • Penrose Cancer Center at Penrose Hospital
  • Porter Adventist Hospital
  • Presbyterian - St. Luke's Medical Center
  • St. Joseph Hospital
  • Rose Medical Center
  • CCOP - Colorado Cancer Research Program
  • Swedish Medical Center
  • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
  • Sky Ridge Medical Center
  • Hope Cancer Care Center at Longmont United Hospital
  • St. Mary - Corwin Regional Medical Center
  • North Suburban Medical Center
  • Mayo Clinic - Jacksonville
  • Tufts-NEMC Cancer Center
  • Mayo Clinic Cancer Center
  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
  • Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplant

Arm Description

Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD).

Outcomes

Primary Outcome Measures

Proportion of Participants With Successful Engraftment

Secondary Outcome Measures

100-day Overall Survival
Proportion of patients who survived 100 days or more after enrolled on the study
Progression-free Survival
Progression-free survival was defined as time from enrollment to disease progression or death from any cause, whichever occurred first. Patients who did not have progression-free survival events were censored at last date of disease assessment.

Full Information

First Posted
April 7, 2003
Last Updated
June 13, 2023
Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00057954
Brief Title
Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma
Official Title
A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplantation for the Treatment of Relapsed Non-Hodgkin and Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
November 9, 2005 (Actual)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet (UV) light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease (GVHD) following bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before bone marrow transplantation. PURPOSE: This phase II trial is studying how well giving photophoresis together with pentostatin and total-body irradiation as a reduced-intensity regimen before allogeneic bone marrow transplantation works in treating patients with relapsed non-Hodgkin's or Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: Determine the rate of stable engraftment of donor cells in patients with relapsed non-Hodgkin's or Hodgkin's lymphoma treated with a reduced toxicity conditioning regimen followed by allogeneic (sibling or unrelated) bone marrow transplantation. Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen. Determine the 100-day overall survival and long-term progression-free survival of patients treated with this regimen. Evaluate the feasibility of collection of molecular chimerism studies at baseline, days 30, 100, 6 months and one and two years and at relapse. OUTLINE: This is a multicenter study. Conditioning regimen: Patients undergo extracorporeal photopheresis using methoxsalen and UV light on 2 consecutive days between days -7 to -4. Patients receive pentostatin intravenously (IV) continuously on days -3 to -2 and undergo total body irradiation on day -1. Allogeneic bone marrow transplantation: Patients undergo infusion of allogeneic bone marrow or stem cells on day 0. Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine beginning on day -1 and continuing until 6 months after transplantation, oral mycofenolate mofetil beginning on day 100 and continuing for 1 year, and methotrexate IV on days 1 and 3. Patients are followed at day 100, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 1.8 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult Hodgkin lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt 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 mycosis fungoides/Sezary syndrome, recurrent adult T-cell leukemia/lymphoma, anaplastic large cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone 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
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transplant
Arm Type
Experimental
Arm Description
Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD).
Intervention Type
Procedure
Intervention Name(s)
Extracorporeal Photopheresis
Other Intervention Name(s)
extracorporeal photochemotherapy
Intervention Description
Day -7 to -4: Extracorporeal Photopheresis may be given as an outpatient therapy on two consecutive days any time between days -7 to -4. This must be performed on UVAR or XTS photopheresis machines (Therakos, Inc.) according to standard procedure as per manufacturer's guidelines.
Intervention Type
Drug
Intervention Name(s)
Pentostatin
Other Intervention Name(s)
DCF,, 2-Deoxycoformycin,, Nipent
Intervention Description
Day -3, -2: Pentostatin 4 mg/m²/d by continuous IV infusion (Total dose = 8 mg/m²)
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation (TBI)
Other Intervention Name(s)
radiation therapy
Intervention Description
Day -1: TBI 400 cGy total dose given in two 200cGy doses. Patients who have received TBI for a previous transplant or radiation as part of previous treatment for a lymphoid malignancy will receive only 200 cGy in 1 dose.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic bone marrow transplantation
Other Intervention Name(s)
allogeneic stem cell transplantation
Intervention Description
Day 0: Infusion of unmanipulated allogeneic bone marrow or stem cells. Minimum cell dose of 2 x 106 CD34 cells/kg recipient and no more than 10 x 10^6 CD34/kg
Intervention Type
Drug
Intervention Name(s)
Cyclosporin (CSA)
Other Intervention Name(s)
Sandimmune,, cyclosporin A,, CSA,, Neoral,, Gengraf
Intervention Description
Cyclosporin A or tacrolimus will be administered according to institutional GVHD prophylaxis protocols. Therapeutic levels will be maintained and patients will be switched to oral agents when they can tolerate
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil (MMF)
Other Intervention Name(s)
Cellcept,, mycophenolic acid,, Lilly-68618,, RS-61443,, MMF
Intervention Description
At day 100 MMF will be introduced at a dose of 250 mg po BID and cyclosporine or tacrolimus will be tapered according to the discretion of the investigator. The dosage will be escalated to a maximum of 2 g/d at the discretion of the attending physician and will be tapered and discontinued at 12 months if there is no active cGVHD. Doses should be given on an empty stomach
Intervention Type
Drug
Intervention Name(s)
Methotrexate (MTX)
Other Intervention Name(s)
Methotrexate sodium,, MTX,, Mexate,, Mexate-AQ,, Folex,, Folex PFS,, Abitrexate,, Rheumatrex,, Amethopterin
Intervention Description
The dose of Methotrexate is based on the corrected ideal body weight for patients with > 33% above ideal weight. Day +1 MTX 15 mg/m² IV push; Day +3 MTX 10 mg/m² IV push (May be omitted if patient develops mouth sores.)
Primary Outcome Measure Information:
Title
Proportion of Participants With Successful Engraftment
Time Frame
Assessed daily during inpatient stay
Secondary Outcome Measure Information:
Title
100-day Overall Survival
Description
Proportion of patients who survived 100 days or more after enrolled on the study
Time Frame
Assessed at least twice a week for the first 60 days and weekly until day 100.
Title
Progression-free Survival
Description
Progression-free survival was defined as time from enrollment to disease progression or death from any cause, whichever occurred first. Patients who did not have progression-free survival events were censored at last date of disease assessment.
Time Frame
Assessed day 100 post transplant and every 3 months during year 1, every 6 months during years 2-3, then every 12 months during years 4-5 or through diagnosis of disease progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Non-Hodgkin's or Hodgkin's lymphoma that has relapsed following either a course of high dose chemotherapy or autologous stem cell transplantation. >= 90 days from prior transplant. Have a suitable human leukocyte antigen (HLA)-matched related bone marrow donor or a compatible matched unrelated bone marrow donor by molecular typing at HLA A, B, C, D, DR. Physically and psychologically capable of undergoing bone marrow transplantation and its attendant period of strict isolation. Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Be able to receive 400 cGy Total Body Irradiation (TBI). Pulmonary function tests: Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO) >= 50% predicted, the forced expiratory volume in 1 second (FEV1) >= 50% predicted. Left ventricular ejection fraction (LVEF) at least 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram. Renal function: creatinine clearance > 50 ml/min. Liver function tests: < 3 x Upper Limit of Normal (ULN). Liver function test include serum glutamic oxaloacetic transaminase (SGOT) (Aspartate transaminase (AST)), Serum Glutamic Pyruvate Transaminase (SGPT) (Alanine transaminase (ALT)), and bilirubin. Exclusion Criteria: Human immunodeficiency virus positive (HIV+) patients (test positive for P21 antibodies to HIV). Evidence of active infection (have received parenteral antibiotics <= 2 weeks prior to registration). Pregnant or breast-feeding women. Curable with any other therapeutic interventions.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francine M. Foss, MD
Organizational Affiliation
Yale University
Official's Role
Study Chair
Facility Information:
Facility Name
Aurora Presbyterian Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Boulder Community Hospital
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80301-9019
Country
United States
Facility Name
Penrose Cancer Center at Penrose Hospital
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80933
Country
United States
Facility Name
Porter Adventist Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
Presbyterian - St. Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
St. Joseph Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rose Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States
Facility Name
CCOP - Colorado Cancer Research Program
City
Denver
State/Province
Colorado
ZIP/Postal Code
80224-2522
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
Facility Name
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
City
Grand Junction
State/Province
Colorado
ZIP/Postal Code
81502
Country
United States
Facility Name
Sky Ridge Medical Center
City
Lone Tree
State/Province
Colorado
ZIP/Postal Code
80124
Country
United States
Facility Name
Hope Cancer Care Center at Longmont United Hospital
City
Longmont
State/Province
Colorado
ZIP/Postal Code
80502
Country
United States
Facility Name
St. Mary - Corwin Regional Medical Center
City
Pueblo
State/Province
Colorado
ZIP/Postal Code
81004
Country
United States
Facility Name
North Suburban Medical Center
City
Thornton
State/Province
Colorado
ZIP/Postal Code
80229
Country
United States
Facility Name
Mayo Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Tufts-NEMC Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma

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