Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

This study is currently recruiting participants.
Verified July 2013 by Stanford University
Sponsor:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT00481832
First received: May 31, 2007
Last updated: July 11, 2013
Last verified: July 2013
  Purpose

The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: Cyclophosphamide
Drug: Carmustine
Drug: Etoposide
Drug: Filgrastim
Drug: Antithymocyte globulin
Drug: Cyclosporine
Drug: Mycophenolate mofetil
Drug: rituximab
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 Stanford University:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of chemotherapy-associated pneumonitis [ Time Frame: 3 months following the enrollment of the last participant. ] [ Designated as safety issue: Yes ]
  • Overall and non-relapse mortality rate [ Time Frame: Two years after the last participant is enrolled ] [ Designated as safety issue: Yes ]
  • Kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: Two years after the last participant is enrolled ] [ Designated as safety issue: Yes ]
  • Incidence and extent of acute and chronic Graft versus host disease [ Time Frame: Two years after the last participant is enrolled. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: January 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hematopoietic cell transplantation
autologous hematopoietic cell transplantation (AHCT) followed by total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) followed by matched allogeneic hematopoietic cell transplantation.
Drug: Cyclophosphamide
4gm/m2and100mg/kg
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Drug: Carmustine
15mg/kg, IV over 2 hours
Other Name: BiCNU
Drug: Etoposide
60mg/kg, IV over 4 hours
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Filgrastim
5-10mcg/kg, SQ
Other Names:
  • G-CSF
  • Neupogen
  • Grafeel
  • Religrast
  • Nugraf
  • Shilgrast
  • Neukine
  • Emgrast
Drug: Antithymocyte globulin
1.5mg/kg/dx5, IV
Other Name: ATG
Drug: Cyclosporine
5mg/kgbid,variable, po or IV
Other Names:
  • cyclosporine
  • cyclosporin
  • cyclosporin A
Drug: Mycophenolate mofetil
15mg/kg,variable, po or iv
Other Names:
  • MMF
  • CellCep
Drug: rituximab
375mg/m2, IV
Other Names:
  • Rituxan
  • MabThera

Detailed Description:

Currently, patients with recurrent or primary refractory non-Hodgkin's lymphoma are treated with second-line chemotherapy (usually 2-3 courses) for the purpose of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells are mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. The standard high dose regimen consists of augmented carmustine, etoposide and cyclophosphamide. 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.

Past studies conducted at Stanford have included a group of 17 patients with transformed lymphoma who received autologous transplants, 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 has been 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. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide and cyclophosphamide 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. Eligible patients must have 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 2nd or greater relapse or 3 or subsequent remission, or 5) 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 BMT Faculty and the Principal Investigator

    • Definition of Minimal Disease State- No individual lymph nodes greater than 2 cm, greater than >75% reduction in a bulky mass (> 10 cm) and < 10% bone marrow involvement with lymphoma.
  • ECOG performance status < 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 registration
  • 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 < 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 = (140Óage)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 must have an echocardiogram or MUGA scan within 42 days of registration. 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 > 50% prior to the autologous transplant and > 40% prior to the allogeneic transplant.
  • Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide 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 active infection requiring oral or intravenous antibiotics are excluded.
  • No prior autologous or allogeneic hematopoietic cell transplantation.
  • No prior radioimmunotherapy
  • Patient with recurrent/refractory diffuse large B cell lymphoma.

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.
  • Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be performed within 30 days of donation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00481832

Contacts
Contact: Physician Referrals (650) 723-0822

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Physician Referrals    650-723-0822      
Sub-Investigator: Laura Johnston         
Sub-Investigator: Ginna Laport         
Sub-Investigator: Robert Lowsky         
Sub-Investigator: David Miklos         
Sub-Investigator: Robert S Negrin         
Sub-Investigator: Judith Anne Shizuru         
Principal Investigator: Wen-Kai Weng         
Sub-Investigator: Youn H Kim         
Sub-Investigator: Sally Arai         
Sub-Investigator: Richard T. Hoppe         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Wen-Kai Weng Stanford University
  More Information

No publications provided

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT00481832     History of Changes
Other Study ID Numbers: BMT185, 97623
Study First Received: May 31, 2007
Last Updated: July 11, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Cyclophosphamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Lenograstim
Rituximab
Carmustine
Etoposide
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antirheumatic Agents
Myeloablative Agonists
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014