Umbilical Cord Blood Transplantation As Treatment Of Adult Patients With Hematologic Disorders

Study Overview
=================
Brief Summary
-----------------
To determine the time to and rate of hematologic engraftment following unrelated umbilical cord blood transplantation in adults with one or two cord blood units using total body irradiation and fludarabine as the transplant conditioning regimen and cyclosporine/MMF as graft-versus-host disease prophylaxis.

Official Title
-----------------
Umbilical Cord Blood Transplantation as Treatment of Adult Patients With Hematologic Disorders

Conditions
-----------------
Hematological Malignancy, Bone Marrow Failure Syndrome

Intervention / Treatment
-----------------
* Drug: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders
* Radiation: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders
* Procedure: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have a histologically confirmed diagnosis at The Vancouver General Hospital or the BCCA-Vancouver. Eligible patients will have one of the following underlying diseases: High risk acute lymphoblastic leukemia (ALL) in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC >100x109/L) or failure to achieve a complete remission after standard induction therapy. Acute myeloid leukemia (AML) in first complete remission with high risk cytogenetics or failure to achieve complete remission after standard induction therapy. ALL or AML in second or subsequent remission Myelofibrosis with myeloid metaplasia. Chronic myeloid leukemia in chronic (failed interferon and/or Gleevec) or accelerated phase. Myelodysplastic syndrome with IPSS risk category >Int-1 Aplastic anemia Non-Hodgkin's lymphoma, chronic lymphocytic leukemia or Hodgkin's disease in relapse or second or subsequent remission. Multiple Myeloma No active central nervous system (CNS) disease. No 9/10 or better HLA antigen matched related donor or VUD available. The patient's condition precludes waiting to search and find a VUD in the Unrelated Donor Registries Acceptance of standard blood product support Adequate organ function as defined by current Leukemia/BMT Program of BC standards (Appendix 10.1) Karnofsky performance status ≥ 80 (Appendix 10.2) Exclusion Criteria: Active infection Pregnancy Significant psychiatric disorder Progressive disease
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders<br>* To determine the time to and rate of hematologic engraftment following unrelated umbilical cord blood transplantation in adults with one or two cord blood units using total body irradiation and fludarabine as the transplant conditioning regimen and cyclosporine/MMF as graft-versus-host disease prophylaxis. DRUG/DOSE DAYS -9 -8, -7 -6 -5 -4 -3 -2 -1 Total Body Irradiation 150 cGy per treatment (1350cGy total) 2x 2x 2x 2x 1x Fludarabine 40mg/m2 10:00am (After TBI) over 60 minutes x x x x Umbilical cord blood infusion (minimum of 24hrs after Flu infusion) x Fludarabine dose adjustment: 70ml/min: decrease dose by Creatinine Clearance 20% Fludarabine dosing will be based on the 40% adjusted ideal body weight. UCB Infusion<br>Radiation: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders<br>* DRUG/DOSE DAYS -9 -8, -7 -6 -5 -4 -3 -2 -1 Total Body Irradiation 150 cGy per treatment (1350cGy total) 2x 2x 2x 2x 1x<br>Procedure: Umbilical Cord Blood Transplantation as Treatment of Adult Patients with Hematologic Disorders<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and efficacy of multiple cord blood transplantation in patients with hematological malignancy. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the 100-day treatment related mortality (TRM), complete remission rate and the 2-year progression free and overall survival rate for patients under going this treatment. |  | 100 days | 
| To determine the incidence of grades II-IV and grades III-IV acute GVHD and incidence of limited and extensive chronic GVHD. |  | 1 year | 
| To measure time to immunologic reconstitution as defined by normal numbers of T and B-cells and normal immunoglobulin synthesis |  | 1 year | 
| To determine rate of hematologic engraftment following umbilical cord blood transplantation with 1-2 cord blood units using total body irradiation & fludarabine as transplant conditioning regimen & cyclosporine/MMF as graft-vs-host disease prophylaxis |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Unrelated Umbilical Cord Blood Transplant, Multiple cord blood