Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients Wtih Advanced Hematopoietic Malignancies

Sponsor

University of California, San Francisco (Other)

Overall Status

Terminated

CT.gov ID

NCT00513318

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplasia Acute Lymphoblastic Leukemia Chronic Myelogenous Leukemia Multiple Myeloma Lymphomas Low-grade NHL and Chronic Lymphocytic Leukemia

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

15 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients Wtih Advanced Hematopoietic Malignancies

Study Start Date :

Aug 1, 2004

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Jun 1, 2009

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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%).
Acute lymphoblastic leukemia not expected to be cured with chemotherapy. This will include patients with high-risk cytogenetics (Ph+, t(4,11), 11q23 abnormalities, and monosomy 7), patients requiring more than one induction course to achieve remission, as well as patients failing to enter remission or in second or subsequent remission. Marrow blasts must be < or equal to 10%. If required, chemotherapy may be given to achieve target level of blasts.
Chronic myelogenous leukemia- chronic phase failing imatinib mesylate therapy (either progressive disease or failure to achieve a major cytogenetic response at 1 year following initiation of therapy), accelerated phase failing to achieve a complete cytogenetic remission at 1 year following initiation of therapy, accelerated phase failing to achieve any cytogenetic response at 6 months of therapy, accelerated phase with progressive disease as demonstrated by worsening cytogenetic response in two consecutive analyses separated by 4 weeks or CML in blast crisis. Patients with blast phase of CML must have < 10% blasts in bone marrow.
Multiple myeloma stage I-III with relapse following autologous transplant, with disease refractory to at least two prior conventional; myeloma therapies or with chromosome 13 abnormalities. Patients with chromosome 13 abnormalities are eligible either at diagnosis or after initial progression.
Lymphomas including diffuse or follicular large cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, T-NK cell lymphoma, or Hodgkin's disease which has failed to respond to primary therapy, progressed, or recurred after prior therapy. Patients who have relapsed following autologous transplant are eligible.
Low-grade NHL and Chronic Lymphocytic Leukemia with relapse or refractory disease following, at least, two chemotherapy-based treatment regimens; or with relapse following autologous transplantation.
Patients must have an ECOG PS < or equal to 2.
Laboratory requirements:
Creatinine < 2.0mg/dL and creatinine clearance > 40/m/min (calculated or based on 24-hour urine collection)
Bilirubin <2.0mg/dL, AST/alkphos <3x upper limit of normal
Patients with hepatitis C and active hepatitis B (hepatitis B DNA detectable) are eligible only if a liver biopsy is performed and there is grade < or equal to 2 fibrosis and/or inflammation. Patients with a history of HBV infection should be tested for HBeAg, anti-HBe and HBV DNA (quantitative). Patients with active HBV viral replication should receive anti-viral therapy.
Cardiac ejection fraction > 30%, DLCO > or equal to 40%.
Negative pregnancy test (for females of reproductive age only).
Signed informed consent

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