Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma
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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: Stem cell infusion Procedure: TLI Drug: Anti-thymocyte globulin Drug: Solumedrol Drug: Tacrolimus Drug: Mycophenolate mofetil |
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 |
- Determine the event free survival [ Time Frame: Up to 10 years from transplant ] [ Designated as safety issue: No ]
- Determine the toxicities [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
- To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: Day 56, Day 100, Day 180, and Day 365 ] [ Designated as safety issue: No ]
- To evaluate the incidence and extent of acute and chronic GVHD. [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
- To evaluate the overall and non-relapse mortality rate. [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Incidence of chemotherapy-associated pneumonitis [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 25 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | December 2018 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
Experimental: Allogeneic Transplant
|
Procedure: Stem cell infusion
Procedure: TLI
Drug: Anti-thymocyte globulin
Other Names:
Drug: Solumedrol
Other Names:
Drug: Tacrolimus
Other Names:
Drug: Mycophenolate mofetil
Other Names:
|
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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00882895
| Contact: Keith Stockerl-Goldstein, MD | 314 747-8439 | kstocker@DOM.wustl.edu | |
| Contact: Nick Fisher | 314-454-5102 | nfisher@dom.wustl.edu |
| United States, Missouri | |
| Washington University | Recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: Keith Stockerl-Goldstein, MD 314-747-8439 kstocker@DOM.wustl.edu | |
| Contact: Nick Fisher 314-454-5102 nfisher@dom.wustl.edu | |
| Principal Investigator: Keith Stockerl-Goldstein, MD | |
| Sub-Investigator: Amanda Cashen, M.D. | |
| Sub-Investigator: Nancy Bartlett, M.D. | |
| Sub-Investigator: Camille Abboud, M.D. | |
| Sub-Investigator: John DiPersio, M.D., Ph.D. | |
| Sub-Investigator: Michael Tomasson, M.D. | |
| Sub-Investigator: Geoffrey Uy, M.D. | |
| Sub-Investigator: Ravi Vij, M.D. | |
| Sub-Investigator: Matthew Walter, M.D. | |
| Sub-Investigator: Peter Westervelt, M.D., Ph.D. | |
| Principal Investigator: | Keith Stockerl-Goldstein, MD | Washington University School of Medicine |
More Information
Additional Information:
Publications:
| Responsible Party: | Washington University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT00882895 History of Changes |
| Other Study ID Numbers: | 09-0042 / 201101864 |
| Study First Received: | April 15, 2009 |
| Last Updated: | April 27, 2016 |
| 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 |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Tacrolimus Mycophenolate mofetil Antilymphocyte Serum Mycophenolic Acid Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate |
Methylprednisolone acetate Methylprednisolone Prednisolone hemisuccinate Prednisolone phosphate Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Antineoplastic Agents Anti-Inflammatory Agents Antiemetics Autonomic Agents |
ClinicalTrials.gov processed this record on September 23, 2016