Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients Wtih Advanced Hematopoietic Malignancies
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- University of California, San Francisco
- Enrollment
- 15
- Locations
- 1
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
This is a pilot study designed to evaluate the safety and feasibility of performing umbilical cord blood transplants in older adults or younger infirm patients with high-risk hematopoeitic malignancies. A novel reduced-intensity preparative regimen for umbilical cord blood transplantation will be used. One to a maximum of three cord blood units, depending on cell count, will be administered to facilitate engraftment. Ten patients will be enrolled with an expected accrual rate of 3-4 patients per year and with a goal of completing accrual within 2-3 years.
Detailed Description
Primary Objective: * To assess the feasibility of performing umbilical cord blood transplants in older adults or younger infirm patients using a reduced-intensity preparative regimen. Feasibility of the procedure is defined as an engraftment rate of \>80% at Day 180 post-transplantation and a transplant related mortality (TRM) of \<50% at Day 100. A TRM of \>50% will be considered unacceptable. Secondary objectives: * To describe the time to neutrophil and platelet recovery following mini-UCB transplantation. * To assess lineage-specific chimerism following transplantation and to describe the contribution of each individual CB unit to post-transplantation hematopoeisis. * To describe disease-specific, event-free and overall survival rates at 180 and 360 days. * To describe the incidence, severity, and timing of acute and chronic GVHD following reduced-intensity UCB transplantation. * To evaluate T-cell, B-cell, and NK cell recovery following reduced-intensity UCB transplantation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 55-70 years, or \< 55 years if deemed ineligible for conventional high dose chemotherapy by the UCSF SCT Committee or by protocol eligibility requirements for myeloablative therapy. Reasons for ineligibility for myeloablative therapy include:
- •Poor cardiac function (i.e. LVEF \< 40%)
- •Poor pulmonary function (i.e. DLCO \< 50%)
- •Hepatic dysfunction
- •Prior myeloablative therapy
- •Availability of donor cord blood (one to three units) matching at \> or equal to 4 of 6 HLA antigens (A, B, and DR). HLA class I antigens will be determined by serologic methods, and Class II antigens will be determined by high-resolution DNA typing. Typing will be confirmed by the UCSF Immunogenetics Department. The target UCB TNC dose is \> or equal to 3.5 x 10(7) TNC/kg recipient weight, however the absolute minimum TNC requirement is \> 2.5 x 10(7) TNC per kilogram) based on cell counts prior to cryopreservation. Cord blood units will be obtained from all available international banks.
- •HLA identical or 1 antigen mismatched related donors or potential HLA-matched unrelated donors (MUD) must NOT be readily available
- •Disease types include:
- •Acute myeloid leukemia not expected to be curable with chemotherapy. This will include patients with high-risk cytogenetics (-7, -7q, -5, -5q, t(6, 9), t(9, 11), complex (\> or equal to 3 abnormalities), Ph(+), evolution from prior myelodysplasia or AML secondary to prior chemotherapy, failure to achieve remission, second, or subsequent remission or refractory relapse. Marrow blasts must be \< or equal to 10%. This may be achieved using standard chemotherapy treatment.
- •Myelodysplasia with high-risk features. This will include patients with IPSS category INT2 or HI-risk MDS or CMML. Marrow blasts must be \< or equal to 20%. If required, chemotherapy may be given to achieve target levels of blasts. Patients are expected to have disease control or not rapidly progressive disease regardless of blast count (but must be \< or equal to 20%).
Exclusion Criteria
- •Active infection requiring ongoing antibiotic treatment
- •HIV infection
- •Poor performance status (ECOG \> 2)
- •Opinion of BMT Committee that autologous SCT or conventional therapy would be a preferable form of treatment
- •Organ function is below requirements
- •Pregnancy, or breast-feeding
Outcomes
Primary Outcomes
Not specified