Randomized HaploCord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation for Hematologic Malignancies

A Randomized Study of Combined Haplo-identical Umbilical Cord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies

The purpose of this study is compare the efficacy of haplo-cord transplant (investigational arm) with that of a more commonly used procedure in which only the cells contained in one or two umbilical cords are infused (standard arm).

We hypothesize that reduced intensity conditioning and haplo-cord transplant results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic graft versus host disease, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay and promising long term outcomes. We also hypothesize that umbilical cord blood selection can prioritize matching and better matched donors can be identified rapidly for most subjects.

This is a clinical trial for subjects with hematologic malignancies ( acute myelogenous leukemia, acute lymphocytic leukemia, Hodgkin's or Non-Hodgkin's lymphoma, or myelodysplastic syndrome) who are in need of a donor stem cell transplant, and for whom an umbilical cord blood transplant is thought to be the best option. For allogeneic transplant donors, we typically try to use related family members, such as brothers or sisters, or volunteer donors who are 'HLA matched', i.e. share similar proteins on their cells. This study is for subjects for whom such a matched sibling donor or a matched unrelated donor is not available.

This study tests a new method of bone marrow transplantation called combined haplo-identical cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares half of the HLA proteins ( haplo-identical)are collected from the blood, as well as cells from an umbilical cord, and then both are transplanted. It is hoped that by using cells from a haplo-identical relative, subjects will have a faster recovery and require fewer transfusions. Over time the haplo-identical cells from the relative are replaced by the cells from the cord blood. The combined transplantation of haplo-identical stem cells and cord blood has previously been used in approximately 60 subjects with very encouraging results.

The purpose of this study is to compare the efficacy of haplo-cord transplant ( "investigational" arm) with the more commonly used procedure in which only the cells contained in one or two umbilical cords are infused ("standard" arm). Subjects will be randomly assigned into either the haplo-cord group or the umbilical cord group.

If randomized to the haplo-cord group, a family member will undergo a stem cell collection. In both arms, subjects will receive a "conditioning regimen" prior to transplantation. The conditioning regimen consists of chemotherapy, which is meant to destroy the cancer cells and suppress the immune system to allow the transplanted cells to grow. Subjects will remain in the hospital until the stem cells are fully recovered, which is usually 4 to 6 weeks after the transplant. Subjects will have bone marrow aspiration and biopsy at 3 weeks, 4 weeks, 2 months, 6 months and 1 year after the transplant and then yearly thereafter. Participation in the study will continue for up to 5 years after transplantation.

Inclusion Criteria:

1. Subject must have a histologically or cytologically confirmed diagnosis of: Acute Myelogenous Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Lymphoma (Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma)

2. Must be > 18 years of age

3. Subject is likely to benefit from allogeneic transplant in the opinion of the transplant physician

4. An human leukocyte antigen (HLA)-identical related or unrelated donor cannot be identified within an appropriate time frame

5. Karnofsky Performance Status (KPS) of > 80

6. Subject has acceptable organ and marrow function as defined below: Serum bilirubin < 2.0mg/dL ALT(SGPT) 3 X upper limit of normal Creatinine Clearance > 50 mL/min as estimated by the modified MDRD equation.18

7. Ability to understand and the willingness to sign a written informed consent document.

8. A preliminary search has identified both:

   1. Appropriate umbilical cords for a single, or if necessary a double umbilical cord blood (UCB) transplant AND
   2. An appropriate single UCB as well as an appropriate haplo donor for haplo-cord transplant

Exclusion Criteria:

1. Myeloproliferative disorders, hemoglobinopathies, severe aplastic anemia or any diagnosis not listed under 3.1.1
2. Life expectancy is severely limited by concomitant illness or uncontrolled infection
3. Subjects with severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFTs)
4. Subject has evidence of chronic active hepatitis or cirrhosis
5. Subject is HIV-positive
6. Subject is pregnant or lactating. -