Brief Title
Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match
Official Title
A Phase II Study Of Pooled Unrelated Donor Umbilical Cord Blood (UCB) Transplant For Patients With Hematologic Malignancies Needing Allogeneic Stem Cell Transplant But Do Not Have A Related HLA-Matched Donor
Brief Summary
The purpose of this study is to evaluate the multi-lineage hematopoietic chimerism for
unrelated umbilical cord blood (UCB) grafts pooled from two to three cord blood units. Also
to evaluate the toxicity, and antitumor responses of pooled unrelated UCB transplants.
Detailed Description
Hematopoietic stem cell (HSC) transplantation, using human HLA-matched sibling or unrelated
bone marrow or peripheral blood stem cell donor, has been used successfully to treat patients
with high-risk or relapsed hematologic malignancies. However, use of this therapy has been
limited by availability of fully HLA-matched donors, despite the increasing size of unrelated
donor registries. For those transplanted with unrelated donor marrow stem cells, increased
HLA disparity adversely affects survival due to increased risks of severe acute and chronic
graft-versus-host disease (GVHD) and opportunistic infection. Only young recipients are able
to tolerate a single HLA-A, B, DRB1 mismatch in this setting (1-3). To potentially extend the
donor pool, UCB has been used as an alternative source of HSC. Since the first unrelated
donor UCB transplant in 1993, UCB transplants have been performed worldwide. It has been
found to produce outcome comparable to those from matched unrelated HSC in patients with
hematologic malignancies (4). It has been shown that cryopreserved unrelated UCB from 0 to 3
HLA-A, B, DRB1-mismatched donors contains sufficient HSC to engraft most pediatrics and some
adult patients (5-10). Unfortunately, the use of UCB transplant is limited by the small
number of HSC in each of the cord blood unit. This is particularly a problem for adult
patients. It is now possible to pool UBC so that adequate cell numbers are available for
adult transplant (11). UBC is rapidly availability and has very low rate of contamination
with herpes group viruses. UCB transplant results in a low incidence of both severe acute
GVHD and extensive chronic GVHD, despite the use of grafts with substantial donor-recipient
HLA disparity (5-10).
The following conditioning regimens will be used, depending on the underlying hematologic
malignancies. Conditioning regimens with Busulfan/clofarabine and with fludarabine/melphalan
will be used for all patients except those with Non-Hodgkin's lymphoma when the conditioning
regimen of BCNU, Etoposide, ARA-C and Melphalan will be used. GVHD prophylaxis of oral
tacrolimus will be used, depending on the development of GVHD and the clinical conditions of
the patients, tacrolimus may be tapered and discontinued by six months after transplant. The
hematopoietic stem cells from the donors will be infused within 48-72 hours of completing the
chemotherapy. The patients will receive supportive care as indicated including antibiotics,
antivirals, antifungals, anti-seizure, anti-emetic medications and other medications as
necessary. In addition patients will receive irradiated blood products for support as
necessary.CMV negative recipient transplant will receive only CMV- blood products. Neutrophil
engraftment will be defined as the day on which the ANC rises to > 500 cells/ml for two
consecutive days. Platelet engraftment will be defined as the first day on which the platelet
count rises to > 20,000/ml over a 7-day interval without transfusion support.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
evaluate the multi-lineage hematopoietic chimerism for unrelated UCB grafts pooled from two to three cord blood units
Secondary Outcome
evaluate the antitumor responses of pooled UCB transplant
Condition
Acute Myelogenous Leukemia
Intervention
Busulfan
Study Arms / Comparison Groups
Single Arm
Description: The following conditioning regimens will be used, depending on the underlying hematologic malignancies. Conditioning regimens with Busulfan/clofarabine and with fludarabine/melphalan will be used for all patients except those with Non-Hodgkin's lymphoma when the conditioning regimen of BCNU, Etoposide, ARA-C and Melphalan will be used.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1
Start Date
November 2011
Completion Date
November 2013
Primary Completion Date
November 2013
Eligibility Criteria
Inclusion Criteria:
- Patients < 65 years with hematologic malignancies needing stem cell transplant but do
not have HLA-matched sibling donor. Patients with the following diagnosis will be
included:
- AML in first or subsequent complete or partial remissions
- ALL in first or subsequent complete or partial remissions
- CLL in second remission or more advanced disease
- CML who has failed tyrosine kinase inhibitors
- Hodgkin's disease who relapse after autologous transplant
- Non-Hodgkin's lymphoma who relapse after autologous transplant or NK-cell
lymphoma in CR1
- Aplastic anemia patients
- Multiple myeloma in second remission or moer advanced disease, including those
who have failed an autologous transplant
- Myelodysplastic syndrome in first or subsequent complete or partial remission
- Patients must have 6/6, 5/6 or 4/6 molecular matches from unrelated UCB donors.
Matching will be done for A, B, and DR. Matching at DR will be confirmed by molecular
typing.
- Patients must be documented to be HIV negative. Screening must have been performed
within previous 6 months.
- Patients must be able to give written consent.
Exclusion Criteria:
- Patient is excluded if all of the Inclusion criteria above isn't met.
Gender
All
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Seah Lim, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01500161
Organization ID
1127920
Responsible Party
Principal Investigator
Study Sponsor
Texas Oncology Cancer Center
Study Sponsor
Seah Lim, MD, Principal Investigator, Texas Oncology - Amarillo,TX
Verification Date
November 2013