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Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma
This study is not yet open for participant recruitment.
Verified by Washington University School of Medicine, April 2009
First Received: April 15, 2009   Last Updated: April 21, 2009   History of Changes
Sponsored by: Washington University School of Medicine
Information provided by: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00882895
  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: Autologous Transplant
Procedure: Allogeneic Transplant
Phase II

MedlinePlus related topics: Lymphoma
Drug Information available for: Etoposide Etoposide phosphate Filgrastim
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title: Autologous Followed by Non-Myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

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

Primary Outcome Measures:
  • To determine the event-free survival in patients with high-risk non-Hodgkin's lymphoma treated with autologous hematopoietic cell transplantation followed by TLI/ATG followed by matched allogeneic hematopoietic cell transplantation. [ Time Frame: 14 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: At 2, 4, 8, and 14 weeks and 6, 12, and 24 months post allogeneic transplantation ] [ Designated as safety issue: No ]
  • To evaluate the incidence and extent of acute and chronic GVHD. [ Time Frame: 14 Years ] [ Designated as safety issue: Yes ]
  • To evaluate the overall and non-relapse mortality rate. [ Time Frame: 14 Years ] [ Designated as safety issue: Yes ]
  • To evaluate the incidence of chemotherapy-associated pneumonitis. [ Time Frame: 14 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: June 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
One Arm: Autotransplant followed by Allogeneic Transplant
Procedure: Autologous Transplant

BEAM Conditioning:

  1. BCNU: 300mg/m2 IV over 2 hours IV day -7
  2. Etoposide: 100mg/m2 IV over 1 hour IV BID days -6,-5,-4,-3
  3. Cytarabine:100mg/m2 IV over 1 hour IV BID days,-6,-5,-4,-3
  4. Melphalan: 140mg/m2 IV over 30 minutes IV day -2

Autologous Transplant

  1. Minimum of 2 x 10E6 CD34+ cell/kg, goal > 5 x 10E6 CD34+ cell/kg
  2. G-CSF 5 mcg/kg Day +5 until hematologic recovery
Procedure: Allogeneic Transplant

Minimum of 2 months following autologous transplant

TLI/ATG Conditioning:

  1. Total Lymphoid Irradiation (TLI) 80 cGy/day Day -14,-11,-10,-9,-8,-7,-4,-3,-2,-1
  2. Antithymocyte globulin (ATG) 1.5 mg/kg/day IV Day -11,-10,-9,-8,-7
  3. Methylprednisolone 1 mg/kg/day IV Day -11,-10,-9,-8,-7

Stem Cell Infusion Day 0

Immunosuppression:

  1. Tacrolimus po start Day -3
  2. Mycophenolate Mofetil start Day 0

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
  • Relapse after achieving initial remission or failure to achieve initial remission. Patients with residual radiographic abnormalities after primary therapy are eligible if abnormalities are FDG-PET positive. Patients in groups 5 or 6 are eligible for the protocol if they are in first complete remission.
  • Eligible patients must have either

    1. transformed lymphoma
    2. mycosis fungoides that is resistant or refractory to therapy
    3. other histological subtypes in patients that do not have adequate cytoreduction to salvage chemotherapy to reach a minimal disease state
    4. patients in 3rd or greater relapse or subsequent remission
    5. patients with aggressive T-cell lymphomas or
    6. other patients with non-Hodgkin's lymphoma felt to have less than a 20% chance of event-free survival with autologous transplant after discussion with the Lymphoma Faculty and the Principal Investigator
  • ECOG performance status < or = 2
  • Matched related or unrelated donor identified and available. Donor must be a complete match or have only a single allele mismatch.
  • Bone marrow biopsy and cytogenetic analysis within 8 weeks of baseline
  • Women of child-bearing potential and sexually active males must use an accepted and effective method of birth control.
  • Patients must have a pretreatment serum bilirubin < or = 2 x the institutional ULN, a serum creatinine < or = 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min
  • Patients must have an EKG within 42 days prior to baseline that shows no significant abnormalities that are suggestive of active cardiac disease.
  • Patients must have an echocardiogram or MUGA scan within 42 days of baseline. If the ejection fraction is <40%, the patient will not be eligible.

If the ejection fraction is 40-50%, patients must have an exercise echocardiogram or dobutamine-echo with a normal response to exercise.

  • Patients must have a corrected diffusion capacity > or = 50% prior to the autologous transplant and > or = 40% prior to the allogeneic transplant.
  • 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.
  • Have a related or unrelated HLA identical donor who is in good health and have no contra-indications for donation according to standard of care criteria.

Exclusion Criteria

  • Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide.
  • Pregnant or breast-feeding women due to the known birth defects association with the treatments used in this study.
  • Patients known to be human immunodeficiency virus (HIV)-positive because the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population. The antibody test for HIV must be performed within 42 days of baseline.
  • No chemotherapy should be administered within 2 weeks of the initiation of protocol therapy.
  • No 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.
  • Patients with active infection requiring oral or intravenous antibiotics.
  • No prior autologous or allogeneic hematopoietic cell transplantation.
  • No prior radioimmunotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882895

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

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Keith Stockerl-Goldstein, MD Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine ( Keith Stockerl-Goldstein, MD )
Study ID Numbers: 09-0042
Study First Received: April 15, 2009
Last Updated: April 21, 2009
ClinicalTrials.gov Identifier: NCT00882895     History of Changes
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

Study placed in the following topic categories:
Melphalan
Immunoproliferative Disorders
Immunologic Factors
Methylprednisolone
Carmustine
Methylprednisolone acetate
Prednisolone acetate
Tacrolimus
Immunosuppressive Agents
Etoposide phosphate
Antilymphocyte Serum
Lymphoma, Small Cleaved-cell, Diffuse
Lymphatic Diseases
Prednisolone
Mycophenolate mofetil
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Etoposide
Cytarabine
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Lymphatic Diseases
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on May 06, 2009