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

NCT ID: NCT01500161

Last Updated: 2013-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2013-11-30

Brief Summary

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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

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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.

Conditions

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Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia Hodgkins Disease Non-Hodgkins Lymphoma Aplastic Anemia Multiple Myeloma Myelodysplastic Syndrome

Keywords

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Leukemia Lymphoma Myeloma Aplastic Anemia Myelodysplasia AML ALL CLL CML

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

Clofarabine

Intervention Type DRUG

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

Fludarabine

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

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

Carmustine

Intervention Type DRUG

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

Etoposide

Intervention Type DRUG

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

Cytarabine

Intervention Type DRUG

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

Interventions

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Busulfan

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

Intervention Type 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)

Intervention Type 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)

Intervention Type DRUG

Melphalan

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

Intervention Type DRUG

Carmustine

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

Intervention Type DRUG

Etoposide

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

Intervention Type DRUG

Cytarabine

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Texas Oncology Cancer Center

INDUSTRY

Sponsor Role lead

Responsible Party

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Seah Lim M.D.

Principle Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Seah Lim, MD

Role: PRINCIPAL_INVESTIGATOR

Texas Oncology - Amarillo,TX

Locations

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Texas Oncology

Amarillo, Texas, United States

Site Status

Countries

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United States

References

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Balduzzi A, Gooley T, Anasetti C, Sanders JE, Martin PJ, Petersdorf EW, Appelbaum FR, Buckner CD, Matthews D, Storb R, Sullivan KM, Hansen JA. Unrelated donor marrow transplantation in children. Blood. 1995 Oct 15;86(8):3247-56.

Reference Type BACKGROUND
PMID: 7579422 (View on PubMed)

Petersdorf EW, Longton GM, Anasetti C, Martin PJ, Mickelson EM, Smith AG, Hansen JA. The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation. Blood. 1995 Aug 15;86(4):1606-13.

Reference Type BACKGROUND
PMID: 7632970 (View on PubMed)

Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, Gerson SL, Lazarus HM, Cairo M, Stevens CE, Rubinstein P, Kurtzberg J. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001 Jun 14;344(24):1815-22. doi: 10.1056/NEJM200106143442402.

Reference Type BACKGROUND
PMID: 11407342 (View on PubMed)

Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet. 1995 Jul 22;346(8969):214-9. doi: 10.1016/s0140-6736(95)91268-1.

Reference Type BACKGROUND
PMID: 7616801 (View on PubMed)

Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK, McGlave PB, Sender L, Cairo MS. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood. 1996 Aug 1;88(3):795-802.

Reference Type BACKGROUND
PMID: 8704232 (View on PubMed)

Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC, Ciocci G, Carrier C, Stevens CE, Rubinstein P. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med. 1996 Jul 18;335(3):157-66. doi: 10.1056/NEJM199607183350303.

Reference Type BACKGROUND
PMID: 8657213 (View on PubMed)

Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M, Chastang C. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med. 1997 Aug 7;337(6):373-81. doi: 10.1056/NEJM199708073370602.

Reference Type BACKGROUND
PMID: 9241126 (View on PubMed)

Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, Berkowitz RL, Cabbad M, Dobrila NL, Taylor PE, Rosenfield RE, Stevens CE. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med. 1998 Nov 26;339(22):1565-77. doi: 10.1056/NEJM199811263392201.

Reference Type BACKGROUND
PMID: 9828244 (View on PubMed)

Other Identifiers

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1127920

Identifier Type: -

Identifier Source: org_study_id