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

This study has been terminated.
(Insufficient accruals)
Sponsor:
Information provided by (Responsible Party):
Seah Lim M.D., Texas Oncology Cancer Center
ClinicalTrials.gov Identifier:
NCT01500161
First received: November 18, 2011
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Texas Oncology Cancer Center:

Primary Outcome Measures:
  • evaluate the multi-lineage hematopoietic chimerism for unrelated UCB grafts pooled from two to three cord blood units [ Time Frame: Will be tested after granulocyte engraftment - which will happen at an average of 28 days post-transpant ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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 [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 1
Study Start Date: November 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500161

Locations
United States, Texas
Texas Oncology
Amarillo, Texas, United States, 79106
Sponsors and Collaborators
Texas Oncology Cancer Center
Investigators
Principal Investigator: Seah Lim, MD Texas Oncology - Amarillo,TX
  More Information

Publications:

Responsible Party: Seah Lim M.D., Principle Investigator, Texas Oncology Cancer Center
ClinicalTrials.gov Identifier: NCT01500161     History of Changes
Other Study ID Numbers: 1127920
Study First Received: November 18, 2011
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Texas Oncology Cancer Center:
Leukemia
Lymphoma
Myeloma
Aplastic Anemia
Myelodysplasia
AML
ALL
CLL
CML

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Myeloproliferative Disorders
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 24, 2014