Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
Conditions
Lymphoma, Non-Hodgkin
Conditions: official terms
Lymphoma - Lymphoma, Non-Hodgkin
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cyclophosphamide Type: Drug
Name: Carmustine Type: Drug
Name: Etoposide Type: Drug
Name: Filgrastim Type: Drug
Name: Antithymocyte globulin Type: Drug
Name: Cyclosporine Type: Drug
Name: Mycophenolate mofetil Type: Drug
Name: rituximab Type: Drug
Overall Status
Recruiting
Summary
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.
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 70 Years
Minimum Age: 18 Years
Gender: Both
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.
Location
Stanford University School of Medicine
Stanford, California, United States
Status: Recruiting
Contact: Physician Referrals - 650-723-0822
Start Date
January 2007
Completion Date
June 2019
Sponsors
Stanford University
Source
Stanford University
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page