Phase II Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00482053
First received: May 31, 2007
Last updated: September 10, 2010
Last verified: September 2010
  Purpose

The purpose of this study is to develop an alternative treatment for patients with relapsed diffuse large B cell lymphoma who are not likely to be cured by the conventional transplantation regimen.


Condition Intervention Phase
Lymphoma, B-Cell
Blood and Marrow Transplant (BMT)
Lymphomas: Non-Hodgkin
Diffuse Large B-Cell
Procedure: Total lymphoid irradiation (TLI)
Drug: Anti-thymocyte globulin (ATG)
Procedure: Allogeneic hematopoietic cell transplantation
Procedure: Autologous hematopoietic cell transplantation (AHCT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study in Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as a Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT)

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • To estimate event-free survival and toxicity in poor risk recurrent or primary refractory DLBCL treated with TLI and ATG followed by matched allogeneic hematopoietic cell transplantation as a consolidation to AHCT [ Time Frame: unknown ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: unknown ] [ Designated as safety issue: No ]
  • To evaluate the incidence and extent of chronic GVHD. [ Time Frame: unknown ] [ Designated as safety issue: No ]
  • To evaluate the overall and transplant related mortality rate. [ Time Frame: unknown ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: October 2006
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Detailed Description:

This purpose of this clinical trial is to develop an alternative treatment for patients with relapsed diffuse large B cell lymphoma who are not likely to be cured by the conventional transplantation regimen. This study tests a tandem transplant approach that starts with transplantation of the patient's own hematopoietic (blood) cells (AHCT) as preparation for an allogeneic transplantation whereby the blood cells from a matched donor are used to try to support the patient's immune system to fight the cancer cells. A novel combination of lymphoma-specific radiation that only impacts the lymphoid organs (lymph nodes and spleen) and an immune suppressing drug is given to prepare the patient body to receive the donor's cells. This conditioning regimen is used because it has been shown to reduce the likelihood of a very common side-effect, known as graft versus host disease, a negative reaction of the donor's cells against the patient's tissues. By carefully preparing the patient for this immune-based strategy, it is hoped that an improvement in event-free survival and a reduction in the risk of disease relapse after AHCT will be seen.

  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 diffuse large B-cell lymphoma (DLBCL) by the WHO classification.
  • 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.
  • Receipt of 2 cycles of second-line therapy and FDG-PET positive per Stanford (central) review. FDG-PET to be done 2 weeks after cycle 2 of second line chemotherapy.
  • ECOG performance status < 2
  • Matched related or unrelated donor identified and available
  • Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration
  • Women of child-bearing potential and sexually active males are strongly advised to use an accepted and effective method of birth control.
  • Patients must have a pretreatment serum bilirubin < 2 x the institutional ULN, a serum creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min by the following formula (all tests must be performed within 28 days prior to registration):

    • Estimated Creatinine Clearance = (140 age)X WT(kg) X 0.85 if female 72X serum creatinine(mg/dl).
  • Patients must have an EKG within 42 days prior to registration that shows no significant abnormalities that are suggestive of active cardiac disease.
  • Patients requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia, or congestive heart failure are not eligible.
  • Patients must have a radionuclide ejection fraction within 42 days of registration. If the ejection fraction is <40%, the patient will not be eligible. If the ejection fraction is 40-50%, the patient will have a cardiology consult.
  • Patients must have a corrected diffusion capacity >55%.
  • Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide are not eligible.
  • Patients with > grade 2 sensory or motor peripheral neuropathy from prior vinca alkaloid use are not eligible.
  • 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:- Pregnant or breast-feeding women are ineligible due to the known birth defects association with the treatments used in this study.

  • Patients known to be human immunodeficiency virus (HIV)-positive are ineligible 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 registration.
  • No chemotherapy other than corticosteroids 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 a prior diagnosis of non-Hodgkin's lymphoma are not eligible.
  • Patients with active infection requiring oral or intravenous antibiotics are excluded.
  • No prior autologous or allogeneic hematopoietic cell transplantation.
  • No prior radioimmunotherapy

Donor Selection/Evaluation:

  • Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation.
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 16 µg/kg of body weight.
  • Donors will be evaluated with a full history and physical examination.
  • Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be performed within 30 days of donation.
  • Prospective donors will be screened for CMV seroreactivity and seronegative donors will be utilized if available. If the possibility of more than one HLA-matched related donor exists, then the donor will be selected on the basis of CD31 allotype.
  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: NCT00482053

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Sandra Jeane Horning Stanford University
  More Information

No publications provided

Responsible Party: Sandra Jeane Horning, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT00482053     History of Changes
Other Study ID Numbers: BMT186, 97355, BMT186
Study First Received: May 31, 2007
Last Updated: September 10, 2010
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on August 01, 2014