Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match

Sponsor

Texas Oncology Cancer Center (Industry)

Overall Status

Terminated

CT.gov ID

NCT01500161

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia Hodgkins Disease Non-Hodgkins Lymphoma Aplastic Anemia Multiple Myeloma Myelodysplastic Syndrome	Drug: Busulfan Drug: Clofarabine Drug: Fludarabine Drug: Melphalan Drug: Carmustine Drug: Etoposide Drug: Cytarabine	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm 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.	Drug: Busulfan Busulfan 3.2 mg/kg/day intravenously on days -7, -6, -5 and -4(for non-NHL patients patients who get Clofarabine regimen) Drug: Clofarabine Clofarabine intravenously 40 mg/m2/day on days -7, -6, -5, -4 and -3(for non-NHL patients patients who get Busulfan regimen) Drug: Fludarabine Fludarabine 30 mg/kg/day intravenously on days -7, -6, -5, -4 and -3 (for non-NHL patients who receive Melphalan containing regimen) Drug: Melphalan Melphalan intravenously 140 mg/m2/day on day -3 (only for non-NHL patients who receive Fludarabine OR for all NHL regimens) Drug: Carmustine BCNU(Carmustine)300 mg/m2 intravenously on day -7 (for NHL patients only) Drug: Etoposide Etoposide 300 mg/m2/day intravenously on days -6, -5, -4 and -3 (for NHL patients only) Drug: Cytarabine ARA-C(Cytarabine) 100 mg/m2/day on days -6, -5, -4 and -3 (for NHL patients only)

Arm

Intervention/Treatment

Experimental: Single Arm

Drug: Busulfan

Busulfan 3.2 mg/kg/day intravenously on days -7, -6, -5 and -4(for non-NHL patients patients who get Clofarabine regimen)

Drug: Clofarabine

Clofarabine intravenously 40 mg/m2/day on days -7, -6, -5, -4 and -3(for non-NHL patients patients who get Busulfan regimen)

Drug: Fludarabine

Fludarabine 30 mg/kg/day intravenously on days -7, -6, -5, -4 and -3 (for non-NHL patients who receive Melphalan containing regimen)

Drug: Melphalan

Melphalan intravenously 140 mg/m2/day on day -3 (only for non-NHL patients who receive Fludarabine OR for all NHL regimens)

Drug: Carmustine

BCNU(Carmustine)300 mg/m2 intravenously on day -7 (for NHL patients only)

Drug: Etoposide

Etoposide 300 mg/m2/day intravenously on days -6, -5, -4 and -3 (for NHL patients only)

Drug: Cytarabine

ARA-C(Cytarabine) 100 mg/m2/day on days -6, -5, -4 and -3 (for NHL patients only)

Outcome Measures

Primary Outcome Measures

evaluate the multi-lineage hematopoietic chimerism for unrelated UCB grafts pooled from two to three cord blood units [Will be tested after granulocyte engraftment - which will happen at an average of 28 days post-transpant]
Blood will be obtained for DNA preparation for VNTR chimerism study post transplant after time of engraftment, which will happen at an average of 28 days post-trasplant.

Secondary Outcome Measures

evaluate the antitumor responses of pooled UCB transplant [Disease staged at baseline, then disease status re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant]
Baseline - All patients will have a detailed history and physical examination, CBC, complete biochemical profile and full staging procedure appropriate for the underlying disease. Post Transplant Evaluation- Disease status will be assessed prior to discharge, again at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months.The following data will be collected: hematologic recovery, and grade and tumor responses and duration of response.
Number of participants that develop Graft Versus Host Disease after pooled UCB transplant [Patients will be assessed weekly during first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant.]
Baseline - All patients will have a detailed history and physical examination, CBC, complete biochemical profile. Post Transplant Evaluation- Patient will be evaluated prior to discharge,then weekly for first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months. The following data will be collected: Patient will be assessed for any ongoing adverse events, and CBC's and biochemical profile's will be performed.
The Infection rate seen in the participants who received a pooled UCB transplant [Patients will be assessed weekly during first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant.]
Baseline - All patients will have a detailed history and physical examination, CBC, complete biochemical profile. Post Transplant Evaluation- Patient will be evaluated prior to discharge,then weekly for first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months. The following data will be collected: Patient will be assessed for any ongoing adverse events, and CBC's and biochemical profile's will be performed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.