Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
18 Years
70 Years
Both
Lymphoma, Non-Hodgkin
Trial Information
Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
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.
Inclusion 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the event free survival
Outcome Time Frame:
Up to 10 years from transplant
Safety Issue:
No
Principal Investigator
Keith Stockerl-Goldstein, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Washington University School of Medicine
Authority:
United States: Institutional Review Board
Study ID:
09-0042 / 201101864
NCT ID:
NCT00882895
Start Date:
May 2009
Completion Date:
December 2013
Related Keywords:
- Lymphoma, Non-Hodgkin
- Lymphoma, Non-Hodgkin
- Transplantation, Autologous
- Transplantation, Homologous
- Total Lymphoid Irradiation
- Anti-thymocyte globulin
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| Washington University | St. Louis, Missouri 63110 |
