Trial Of Double Umbilical Cord Blood Transplantation

NCT ID: NCT00763490

Last Updated: 2016-12-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2015-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This pilot research study is to investigate the safety and effectiveness of stem cell transplantation to treat blood-related (hematopoietic) cancers, using stem cells collected from two different, umbilical cord blood donors. Subjects in this study are receiving a stem cell transplant because other treatments have failed or their disease is unlikely to respond to other treatment options.

Blood-related cancers can be treated and sometimes cured with very high doses of chemotherapy and radiation therapy, given to kill the cancer cells; however, these treatments can prove unsuccessful and can harm normal cells in the bone marrow or a patient's disease may be unlikely to respond to these treatment options.

Hematopoietic stem cells transplantation (HSCT) is a potential cure, but opportunities to perform HSCT are limited by donor availability. Only 20-30% of patients may have matched family donors. In some cases, a mismatched family donor may be suitable. For patients needing a transplant who do not have a suitably matched family donor, blood stem cells from matched unrelated donors can be used. The length of time required to identify a matched unrelated donor presents another obstacle for patients waiting to receive an HSCT.

Blood stem cells are found in umbilical cord blood (UCB), which is blood left over in the placenta (afterbirth) after a baby is born. Usually this blood is discarded with the placenta, but over the past 15 years, we have learned how to collect and freeze cord blood cells to be used for transplants at a later time. A cord blood unit is the cord blood cells collected and stored from a single placenta. More than 6,500 umbilical cord blood stem cell transplants have been done worldwide, mostly in children with leukemia. One important factor affecting the success of a cord blood transplant is the cell dose (number of stem cells in the cord blood unit / recipient's weight). Patients who receive a high cell dose (\> 2.5 x 107 cells/kilogram) have better marrow recovery and a higher rate of survival than those who receive a lower cell dose.

In an attempt to make UCB transplantation possible for bigger children, adolescents and adults, researchers have tried giving two cord blood units on the same day for their transplant, one after the other. The data from more than 150 "double cord blood" transplants in adults suggest that the "double cord blood" transplants may allow bone marrow recovery and survival in patients who do not have a single cord blood unit with enough cells for successful transplantation.

This is a pilot study to research the safety and effectiveness of using two UCB units in adult and pediatric UCB transplantation when combined with a conditioning regimen called Flu/Bu4/TLI (consisting of fludarabine, busulfan and total lymphoid irradiation).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hematological Malignancies

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

umbilical cord blood stem cell transplant leukemia multiple myeloma lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Double cord blood transplant

'full intensity, double umbilical cord, stem cell transplant' with 'Flu/Bu4 conditioning regimen'

Group Type EXPERIMENTAL

Full intensity, double umbilical cord, stem cell transplant

Intervention Type PROCEDURE

stem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation

Flu/Bu4 conditioning regimen

Intervention Type DRUG

Fludarabine: 40 mg/m² daily on days -5, -4, -3, -2

Busulfan: 3.2 mg/kg IV daily on days -5, -4, -3, -2

Total Lymphoid Irradiation (TLI)

Intervention Type RADIATION

one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion

Graft versus Host Disease prevention (GVHD prophylaxis)

Intervention Type DRUG

Tacrolimus for GVHD (Graft Versus Host Disease Prevention) Tacrolimus - will begin on day -3 (IV or oral) for at least 180 days. Target trough level for tacrolimus is 8-12 ng/ml. In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant.

Mycophenolate Mofetil

Intervention Type DRUG

Mycophenolate Mofetil (MMF) for GVHD prophylaxis. MMF - will be given at a dose of 10mg/kg IV q 8 hours if the patient weight is more than 50 kg, or 15 mg/kg IV q 8 hours if less than 50 kg, beginning the morning of day -3. (If renal failure and Glomerular Filtration Rate (GFR) \< 25 mL/min, the dose should not exceed 1 gm every 8 hours. (No dose adjustment for liver disease is required.) MMF should be given via IV until oral medications are tolerated.

MMF will be stopped at Day +28 if no acute GVHD is seen by that time. If there is not any donor cell engraftment, MMF will be continued as directed by the attending physician. If the patient has active acute GVHD requiring systemic therapy, MMF may be continued.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Full intensity, double umbilical cord, stem cell transplant

stem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation

Intervention Type PROCEDURE

Flu/Bu4 conditioning regimen

Fludarabine: 40 mg/m² daily on days -5, -4, -3, -2

Busulfan: 3.2 mg/kg IV daily on days -5, -4, -3, -2

Intervention Type DRUG

Total Lymphoid Irradiation (TLI)

one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion

Intervention Type RADIATION

Graft versus Host Disease prevention (GVHD prophylaxis)

Tacrolimus for GVHD (Graft Versus Host Disease Prevention) Tacrolimus - will begin on day -3 (IV or oral) for at least 180 days. Target trough level for tacrolimus is 8-12 ng/ml. In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant.

Intervention Type DRUG

Mycophenolate Mofetil

Mycophenolate Mofetil (MMF) for GVHD prophylaxis. MMF - will be given at a dose of 10mg/kg IV q 8 hours if the patient weight is more than 50 kg, or 15 mg/kg IV q 8 hours if less than 50 kg, beginning the morning of day -3. (If renal failure and Glomerular Filtration Rate (GFR) \< 25 mL/min, the dose should not exceed 1 gm every 8 hours. (No dose adjustment for liver disease is required.) MMF should be given via IV until oral medications are tolerated.

MMF will be stopped at Day +28 if no acute GVHD is seen by that time. If there is not any donor cell engraftment, MMF will be continued as directed by the attending physician. If the patient has active acute GVHD requiring systemic therapy, MMF may be continued.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* The candidate must have an incurable hematological malignancy or non-malignant hematological disorder and be eligible for transplant by the University of Michigan program.
* The candidate must have a life expectancy of less than one year without transplantation.
* The candidate must have two partially HLA-matched UCB (cord blood) units.Units must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing) loci. Units must be HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with each other (using same resolution of molecular typing as indicated above).
* The candidate must have access to two appropriately HLA-matched units that are available such that one unit delivers a pre-cryopreserved nucleated cell dose of at least 2.5 x 107 per kilogram and the second unit at least 2.0 x 107 per kilogram.

Exclusion Criteria

* The candidate is an adult or pediatric patient who has a suitable related or unrelated donor available for transplant. Suitable donors include 8/8 (HLA-A,B,C and DR, with all loci high-resolution typing) or 7/8 related or unrelated donor available within 42 days of search initiation.
* The candidate has a Karnofsky (Adult) or Lansky (Pediatrics) performance status of \< 70% at the time of admission for HSCT.
* The candidate is a patient with evidence of HIV infection.
* The candidate is a patient with active bacterial, fungal or viral infection not responding to treatment. Non-response to treatment is determined by body temperature, blood culture results, and radiographic findings as applicable.
* The candidate is pregnant.
* The candidate has any medical comorbidities/conditions that, in the opinion of the transplant team, would keep the patient from complying with the needs of the protocol and/or would markedly increase the morbidity and mortality from the procedure.
* The candidate has any conditions, in the opinion of the transplant team, such as substance abuse, or severe personality disorder that would keep the patient from complying with the needs of the protocol and would markedly increase the morbidity and mortality from the procedure.
Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Daniel M Couriel, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Abedin S, Peres E, Levine JE, Choi S, Yanik G, Couriel DR. Double umbilical cord blood transplantation after novel myeloablative conditioning using a regimen of fludarabine, busulfan, and total lymphoid irradiation. Biol Blood Marrow Transplant. 2014 Dec;20(12):2062-6. doi: 10.1016/j.bbmt.2014.07.014. Epub 2014 Jul 18.

Reference Type RESULT
PMID: 25046834 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

HUM00017515

Identifier Type: OTHER

Identifier Source: secondary_id

umcc 2007.137

Identifier Type: -

Identifier Source: org_study_id