Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00882895
First received: April 15, 2009
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Procedure: Stem cell infusion
Procedure: TLI
Drug: Anti-thymocyte globulin
Drug: Solumedrol
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Determine the event free survival [ Time Frame: Up to 10 years from transplant ] [ Designated as safety issue: No ]
  • Determine the toxicities [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: Day 56, Day 100, Day 180, and Day 365 ] [ Designated as safety issue: No ]
  • To evaluate the incidence and extent of acute and chronic GVHD. [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  • To evaluate the overall and non-relapse mortality rate. [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Incidence of chemotherapy-associated pneumonitis [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: May 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Transplant
  • 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)
Procedure: Stem cell infusion Procedure: TLI Drug: Anti-thymocyte globulin
Other Names:
  • ATG
  • Atgam
  • Thymoglobulin
Drug: Solumedrol
Other Names:
  • Medrol
  • Solu-Medrol
Drug: Tacrolimus
Other Names:
  • FK-506
  • Prograf
  • Advagraf
  • Protopic
Drug: Mycophenolate mofetil
Other Names:
  • MMF
  • CellCept
  • Myfortic

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882895

Contacts
Contact: Keith Stockerl-Goldstein, MD 314 747-8439 kstocker@DOM.wustl.edu
Contact: Nick Fisher 314-454-5102 nfisher@dom.wustl.edu

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Keith Stockerl-Goldstein, MD    314-747-8439    kstocker@DOM.wustl.edu   
Contact: Nick Fisher    314-454-5102    nfisher@dom.wustl.edu   
Principal Investigator: Keith Stockerl-Goldstein, MD         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Nancy Bartlett, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: John DiPersio, M.D., Ph.D.         
Sub-Investigator: Tim Graubert, M.D.         
Sub-Investigator: Michael Tomasson, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Matthew Walter, M.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: David Mansur, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Keith Stockerl-Goldstein, MD Washington University Early Recognition Center
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00882895     History of Changes
Other Study ID Numbers: 09-0042 / 201101864
Study First Received: April 15, 2009
Last Updated: June 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Lymphoma, Non-Hodgkin
Transplantation, Autologous
Transplantation, Homologous
Total Lymphoid Irradiation
Anti-thymocyte globulin

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antilymphocyte Serum
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014