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Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma

Primary Purpose

Lymphoma, Non-Hodgkin

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Stem cell infusion
TLI
Anti-thymocyte globulin
Solumedrol
Tacrolimus
Mycophenolate mofetil
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Lymphoma, Non-Hodgkin, Transplantation, Autologous, Transplantation, Homologous, Total Lymphoid Irradiation, Anti-thymocyte globulin

Eligibility Criteria

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

Inclusion Criteria

  • Age 18 to 70 years.
  • Histologically proven non-Hodgkin's lymphoma

  • High risk disease including at least one of the following:

    • Relapsed or refractory disease
    • Transformed lymphoma
    • Aggressive T-cell lymphoma
    • Failure to achieve completed remission (CR) following Auto SCT
    • Less than a 20% chance of event-free survival from autologous transplant determined by the treating physician and the Principal Investigator
  • ECOG performance status < or = 2

  • Underwent Autologous SCT 60-120 days prior to registration including:

    • BEAM conditioning (BCNU: 300 mg/m2 IV day -7, Etoposide: 100 mg/m2 IV BID days -6,-5,-4,-3, Cytarabine: 100 mg/m2 IV BID days -6,-5,-4,-3, Melphalan: 140 mg/m2 IV day -2)
    • Minimum of 2 x 106 CD34+ cells/kg infused

  • Full hematologic recovery following Auto HCT including:

    • Absolute neutrophil count (ANC) >1000 µl
    • Platelet count of ≥50,000 µl independent of transfusion for >7 days
  • Available matched related or unrelated donor. Selected donor must be a complete match or have only a single antigen mismatch.
  • Women of child-bearing potential and sexually active males must use an accepted and effective method of birth control.
  • Bone marrow comprising of < 10% lymphoma on most recent biopsy/aspiration (within 9 months of Allo transplant; may have been performed prior to autologous transplant).
  • Serum bilirubin < or = 2 x the institutional ULN

  • Serum creatinine < or = 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min by the following formula

    • Estimated Creatinine Clearance = (140 age)X WT(kg) X 0.85 if female 72X serum creatinine(mg/dl).
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria

  • Prior autologous or allogeneic hematopoietic cell transplantation (other than autologous SCT 60-120 days prior to registration)
  • Prior radioimmunotherapy
  • Known or suspected progressive disease following autologous SCT
  • Additional treatment for NHL administered from time of autologous SCT through registration
  • Pregnant or breast-feeding women (due to the known birth defects association with the treatments used in this study)
  • Human immunodeficiency virus (HIV)-positive (the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population.)
  • Any prior malignancy is allowed except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years.
  • Active infection requiring oral or intravenous antibiotics.

Inclusion of Women and Minorities

-Both men and women and members of all races and ethnic groups are eligible for this trial.

Sites / Locations

  • Washington University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Transplant

Arm Description

TLI - 80 cGy on days -14, -11, -10, -9, -8, -7, -4, -3, -2, -1 Anti-thymocyte globulin (ATG) 1.5 mg/kg on days -11, -10, -8, -7 Solumedrol - 1 mg/kg on days -11, -10, -9, -8, -7 Tacrolimus - beginning on day -3 with starting dose of 0.3 mg/kg PO BID. Will be continued per institutional guidelines. Stem cell infusion - day 0 Mycophenolate mofetil (MMF) - beginning on day 0 with dose of 15 mg/kg PO (5-10 hours after transplant)

Outcomes

Primary Outcome Measures

Determine the event free survival
Determine the toxicities

Secondary Outcome Measures

To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism.
To evaluate the incidence and extent of acute and chronic GVHD.
To evaluate the overall and non-relapse mortality rate.
Incidence of chemotherapy-associated pneumonitis

Full Information

First Posted
April 15, 2009
Last Updated
January 17, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00882895
Brief Title
Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma
Official Title
Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 5, 2009 (Actual)
Primary Completion Date
June 1, 2028 (Anticipated)
Study Completion Date
June 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a research study testing a new approach to treating high-risk non-Hodgkin's lymphoma consisting of an autologous hematopoietic (blood) stem cell transplant (using a patient's own hematopoietic cells) followed by a non-myeloablative allogeneic transplantation (transplant from another individual). The investigators hypothesize that the addition of the second non-myeloablative transplant will improve the chances for long-term control of lymphoma.
Detailed Description
The approach to recurrent or primary refractory non-Hodgkin's lymphoma has been to treat patients with second-line chemotherapy (usually 2-3 courses) for the purposes of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells have been mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease. In a group of 17 patients with transformed lymphoma who received autologous transplants at Stanford University, the median EFS and OS were 1.48 and 2.7 years respectively with a 7-year survival of only 20%. In comparison, patients with chemosensitive follicular lymphoma who received the same regimen also had a poor median EFS of 1.3 years, but the median survival was 6.7 years. The outcomes for patients with chemotherapy-resistant relapsed NHL is also poor with EFS in the range of 20% in many studies of autologous transplantation. These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that we have taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. In addition, there are limited reports of using an autologous/allogeneic approach for lymphoma patients using non-myeloablative allogeneic transplants. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide, cytarabine and melphalan with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin
Keywords
Lymphoma, Non-Hodgkin, Transplantation, Autologous, Transplantation, Homologous, Total Lymphoid Irradiation, Anti-thymocyte globulin

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Transplant
Arm Type
Experimental
Arm Description
TLI - 80 cGy on days -14, -11, -10, -9, -8, -7, -4, -3, -2, -1 Anti-thymocyte globulin (ATG) 1.5 mg/kg on days -11, -10, -8, -7 Solumedrol - 1 mg/kg on days -11, -10, -9, -8, -7 Tacrolimus - beginning on day -3 with starting dose of 0.3 mg/kg PO BID. Will be continued per institutional guidelines. Stem cell infusion - day 0 Mycophenolate mofetil (MMF) - beginning on day 0 with dose of 15 mg/kg PO (5-10 hours after transplant)
Intervention Type
Procedure
Intervention Name(s)
Stem cell infusion
Intervention Type
Procedure
Intervention Name(s)
TLI
Intervention Type
Drug
Intervention Name(s)
Anti-thymocyte globulin
Other Intervention Name(s)
ATG, Atgam, Thymoglobulin
Intervention Type
Drug
Intervention Name(s)
Solumedrol
Other Intervention Name(s)
Medrol, Solu-Medrol
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK-506, Prograf, Advagraf, Protopic
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Other Intervention Name(s)
MMF, CellCept, Myfortic
Primary Outcome Measure Information:
Title
Determine the event free survival
Time Frame
Up to 10 years from transplant
Title
Determine the toxicities
Time Frame
Day 100
Secondary Outcome Measure Information:
Title
To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism.
Time Frame
Day 56, Day 100, Day 180, and Day 365
Title
To evaluate the incidence and extent of acute and chronic GVHD.
Time Frame
Up to 10 years
Title
To evaluate the overall and non-relapse mortality rate.
Time Frame
Up to 10 years
Title
Incidence of chemotherapy-associated pneumonitis
Time Frame
Day 100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Age 18 to 70 years. Histologically proven non-Hodgkin's lymphoma High risk disease including at least one of the following: Relapsed or refractory disease Transformed lymphoma Aggressive T-cell lymphoma Failure to achieve completed remission (CR) following Auto SCT Less than a 20% chance of event-free survival from autologous transplant determined by the treating physician and the Principal Investigator ECOG performance status < or = 2 Underwent Autologous SCT 60-120 days prior to registration including: BEAM conditioning (BCNU: 300 mg/m2 IV day -7, Etoposide: 100 mg/m2 IV BID days -6,-5,-4,-3, Cytarabine: 100 mg/m2 IV BID days -6,-5,-4,-3, Melphalan: 140 mg/m2 IV day -2) Minimum of 2 x 106 CD34+ cells/kg infused Full hematologic recovery following Auto HCT including: Absolute neutrophil count (ANC) >1000 µl Platelet count of ≥50,000 µl independent of transfusion for >7 days Available matched related or unrelated donor. Selected donor must be a complete match or have only a single antigen mismatch. Women of child-bearing potential and sexually active males must use an accepted and effective method of birth control. Bone marrow comprising of < 10% lymphoma on most recent biopsy/aspiration (within 9 months of Allo transplant; may have been performed prior to autologous transplant). Serum bilirubin < or = 2 x the institutional ULN Serum creatinine < or = 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min by the following formula Estimated Creatinine Clearance = (140 age)X WT(kg) X 0.85 if female 72X serum creatinine(mg/dl). Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria Prior autologous or allogeneic hematopoietic cell transplantation (other than autologous SCT 60-120 days prior to registration) Prior radioimmunotherapy Known or suspected progressive disease following autologous SCT Additional treatment for NHL administered from time of autologous SCT through registration Pregnant or breast-feeding women (due to the known birth defects association with the treatments used in this study) Human immunodeficiency virus (HIV)-positive (the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population.) Any prior malignancy is allowed except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years. Active infection requiring oral or intravenous antibiotics. Inclusion of Women and Minorities -Both men and women and members of all races and ethnic groups are eligible for this trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith Stockerl-Goldstein, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
12855572
Citation
Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W, Storer B, Hegenbart U, Somlo G, Chauncey T, Bruno B, Appelbaum FR, Blume KG, Forman SJ, McSweeney P, Storb R. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood. 2003 Nov 1;102(9):3447-54. doi: 10.1182/blood-2002-09-2955. Epub 2003 Jul 10.
Results Reference
background
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes Jewish Hospital and Washington University School of Medicine

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Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma

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