Trial Of Double Umbilical Cord Blood Transplantation - Full Text View

Sponsored by:	University of Michigan Cancer Center
Information provided by:	University of Michigan Cancer Center
ClinicalTrials.gov Identifier:	NCT00763490

Purpose

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).

Condition	Intervention	Phase
Hematological Malignancies	Procedure: full intensity, double umbilical cord, stem cell transplant Drug: Flu/Bu4 conditioning regimen Radiation: Total Lymphoid Irradiation (TLI) Drug: Graft versus Host Disease prevention (GVHD prophylaxis)	Phase II

MedlinePlus related topics: Cancer Flu Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Fludarabine Fludarabine monophosphate Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Trial Of Double Umbilical Cord Blood Transplantation

Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:

One-year survival rate after transplant [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall and disease free survival at two years and five years [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Incidence of neutrophil and platelet engraftment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Incidence of acute and chronic graft-vs-host disease(GvHD) and relapse [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Correlation between regulatory T cell numbers post-transplant with GVHD outcomes observed during the trial [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	December 2008
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Procedure: 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 Drug: 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 Radiation: Total Lymphoid Irradiation (TLI) one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion Drug: Graft versus Host Disease prevention (GVHD prophylaxis) Co-enrollment on an active U-M study for GVHD prophylaxis is allowed, else a combination of tacrolimus and Mycophenolate Mofetil (MMF). 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. 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 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.

Arms

Assigned Interventions

1: Experimental

Procedure: 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

Drug: 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

Radiation: Total Lymphoid Irradiation (TLI)

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

Drug: Graft versus Host Disease prevention (GVHD prophylaxis)

Co-enrollment on an active U-M study for GVHD prophylaxis is allowed, else a combination of tacrolimus and Mycophenolate Mofetil (MMF).

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.

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 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.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The candidate must have an incurable hematological malignancy and be eligible for transplant by the UM 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 2.0 x 107 per kilogram and the second unit at least 1.5 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763490

Contacts

Contact: Cancer Answer Line

1 (800) 865-1125

canceranswerline@umich.edu

Locations

United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan Cancer Center

Investigators

Principal Investigator:

Edward M Peres, MD

University of Michigan Cancer Center

More Information

Responsible Party:	University of Michigan Cancer Center ( Edward M. Peres, MD / Asst. Professor, Departments of Pediatrics and Int. Medicine )
Study ID Numbers:	umcc 2007.137, HUM00017515
Study First Received:	September 30, 2008
Last Updated:	September 30, 2008
ClinicalTrials.gov Identifier:	NCT00763490
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:

umbilical cord blood
stem cell transplant
leukemia
multiple myeloma
lymphoma

Study placed in the following topic categories:

Leukemia
Multiple myeloma
Hematologic Neoplasms
Hematologic Diseases
Busulfan
Mycophenolate mofetil

Tacrolimus
Fludarabine
Fludarabine monophosphate
Lymphoma
Neoplasms, Plasma Cell
Multiple Myeloma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 14, 2009