Lymphoma Clinical Trial
Official title:
A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using Two Related Donors
This phase II clinical trial studies how well two donors stem cell transplant work in treating patients with high-risk hematologic malignancies. After receiving radiation to help further treat the disease, patients receive a dose of donors' T cells. T cells can fight infection and react against cancer cells. Two days after donors' T cells are given, patients receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not destroyed by CY and they remain in the patient to help fight infection. A few days after the CY is given, patients receive donors' stem cells to help their blood counts recover. Using two donors' stem cell transplant instead of one donor may be more effective in treating patients with high-risk disease and may prevent the disease from coming back.
Status | Terminated |
Enrollment | 4 |
Est. completion date | May 2013 |
Est. primary completion date | February 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Any patient with a hematologic malignancy with residual disease (morphological, cytogenetic, molecular, or radiographic) after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater CR. Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (i.e. <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial. 2. Patients must have two related donors that meet an acceptable scenario as described above. 3. Patients must adequate organ function: - LVEF of >= 50% - DLCO (adjusted for hemoglobin) >= 50% of predicted - Adequate liver function as defined by a serum bilirubin =< 1.8, AST or ALT < 2.5X upper limit of normal - Creatinine clearance of >= 60 ml/min 4. Karnofsky Performance Status of > 80 % on the modified KPS tool (see Appendix A). 5. Patients must be willing to use contraception if they have childbearing potential. 6. Able to give informed consent Exclusion Criteria: 1. Modified KPS of < 80% 2. >= 5 Comorbidity Points on the HCT-CI Index (See Appendix B) 3. Class I or II antibodies against donor HLA antigens 4. HIV positive 5. Active involvement of the central nervous system with malignancy 6. Psychiatric disorder that would preclude patients from signing an informed consent 7. Pregnancy, or unwillingness to use contraception if they have child bearing potential 8. Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder 9. Alemtuzumab treatment within 8 weeks of HSCT admission. 10. ATG level of >= 2 ugm/ml 11. Patients with active inflammatory processes (such as flair of an autoimmune disease) including T max > 101, or active tissue inflammation are excluded. 12. Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Thomas Jefferson University |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | One Year Relapse-Free Survival | To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover. |
1 year | No |
Secondary | Chimerism Assessment | To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment. | 1 year | No |
Secondary | Assessment of Dominance | If dominance is observed, to compare the 2 donors with regard to degree of HLA mismatch, KIR types, CD 34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, NK cell, or other cellular subsets prior to emerging in the graft as a whole. | 1 year | No |
Secondary | Relapse Rates | To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate. | 1 year | No |
Secondary | Engraftment | To assess the consistency and pace of engraftment of both donors. | 1 year | No |
Secondary | Immune Reconstitution | Assess T and B cell Reconstitution | 1 year | No |
Secondary | Non-relapse Morbidity and Mortality | Assessment of regimen related toxicity, GVHD incidence and severity, and overall survival. | 1 year | Yes |
Secondary | Tolerance of DLI | Assessment of the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups | 2-6 days prior to transplant | Yes |
Secondary | Assessment for Tumor Escape Mechanisms | To test for loss of one or both HLA haplotypes in patients who relapse post-transplant and examine the relapse in the context of the characteristics of the 2 donors | 1 year post transplant | No |
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