Hematological MalignanciesPhase 2NCT00763490

Trial Of Double Umbilical Cord Blood Transplantation

A Phase 2 study testing Full intensity, double umbilical cord, stem cell transplant, Flu/Bu4 conditioning regimen and Total Lymphoid Irradiation (TLI) in people with Hematological Malignancies, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 65 years
Conditions the study is for: Hematological Malignancies
What is being tested?: Full intensity, double umbilical cord, stem cell transplant, Flu/Bu4 conditioning regimen and Total Lymphoid Irradiation (TLI)
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: Dec 2008to Oct 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan Cancer Center
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

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).

Conditions: Hematological Malignancies
Being tested: Full intensity, double umbilical cord, stem cell transplant, Flu/Bu4 conditioning regimen, Total Lymphoid Irradiation (TLI), Graft versus Host Disease prevention (GVHD prophylaxis), Mycophenolate Mofetil
Keywords: umbilical cord blood, stem cell transplant, leukemia, multiple myeloma, lymphoma
Medical subject headings: Hematologic Neoplasms, Leukemia, Multiple Myeloma, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Full intensity, double umbilical cord, stem cell transplantProcedure or surgery
stem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation
Flu/Bu4 conditioning regimenDrug
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)Radiation
one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion
Graft versus Host Disease prevention (GVHD prophylaxis)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 MofetilDrug
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.

Study groups in NCT00763490
Study group	Role	What they receive
Double cord blood transplant	Experimental	'full intensity, double umbilical cord, stem cell transplant' with 'Flu/Bu4 conditioning regimen' Receives: 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); Drug: Mycophenolate Mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Alive at 1 Year After Transplant
One-year survival rate after transplant
Measured: 1 year

Secondary outcomes (3)

Percentage of Patients Alive at the End of the Trial
Event Free Survival (EFS) was determined. Patients were followed up to 5 years (median time of 2.35 years).
Measured: 5 Years
Cumulative Incidence of Neutrophil and Platelet Engraftment
The failure to achieve a neutrophil count > 500/uL or a platelet count >30.0 x 10e9 /L within 35 days of the stem cell infusion will be defined as primary engraftment failure.
Measured: Day 35
Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD)
The percentage of patients with acute GVHD (Grade II-IV) was determined at 100 days. Patients were followed up to 5 years and the percentage of patients that developed chronic GVHD at the end of the study was tabulated.
Acute GVHD is staged and graded (grade 0-IV, where grade 0 is no involvement and involvement increases by grade) by the number and extent of organ involvement. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea).
Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2008Oct 2015

First posted1 Oct 2008 (estimated)
Study startDec 2008
Primary completionMar 2013
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hematological MalignanciesStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00763490
Sponsor's protocol ID: umcc 2007.137
Other IDs: HUM00017515
Status last verified: Nov 2016
First submitted: 30 Sep 2008
Last updated: 23 Dec 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 25046834

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hematological Malignancies trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Trial Of Double Umbilical Cord Blood Transplantation
ClinicalTrials.gov ID: NCT00763490
Acronym / sponsor ID: umcc 2007.137
Conditions: Hematological Malignancies
Keywords: umbilical cord blood, stem cell transplant, leukemia, multiple myeloma, lymphoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.
Study start: Dec 2008
Primary completion: Mar 2013 (actual)
Study completion: Oct 2015 (actual)
First posted: 1 Oct 2008 (estimated)
Results: Posted 12 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Double cord blood transplant	Experimental	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), Drug: Mycophenolate Mofetil'full intensity, double umbilical cord, stem cell transplant' with 'Flu/Bu4 conditioning regimen'

Who may qualify

Ages: Up to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Full intensity, double umbilical cord, stem cell transplantstem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation	Procedure or surgery	Double cord blood transplant
Flu/Bu4 conditioning regimenFludarabine: 40 mg/m² daily on days -5, -4, -3, -2 Busulfan: 3.2 mg/kg IV daily on days -5, -4, -3, -2	Drug	Double cord blood transplant
Total Lymphoid Irradiation (TLI)one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion	Radiation	Double cord blood transplant
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.	Drug	Double cord blood transplant
Mycophenolate MofetilMycophenolate 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.	Drug	Double cord blood transplant

Primary outcome

Percentage of Participants Alive at 1 Year After Transplant
Time frame: 1 year
One-year survival rate after transplant

3 secondary outcomes

Percentage of Patients Alive at the End of the Trial
Time frame: 5 Years
Cumulative Incidence of Neutrophil and Platelet Engraftment
Time frame: Day 35
Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD)
Time frame: Up to 5 years

Results and safety

Results posted to the registry on 12 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Double Cord Blood Tranplant	20	20

Primary outcome: Percentage of Participants Alive at 1 Year After Transplant

Time frame: 1 year. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Double Cord Blood Tranplant n = 20
Value	40 (19 to 60)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Double Cord Blood Tranplant	14 of 20 (70%)	8 of 20 (40%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25046834Abedin 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.

Related trials for Hematological Malignancies

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MACE and BTK Inhibitors
Hematologic Cancer, MACE
RecruitingEarly Phase 1
HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Hematologic Malignancy
Recruiting
An Exploratory Study to Evaluate Immune Determinants of the Response to Adoptive Cell Therapy (ACT) in Solid and Hematologic Tumors
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RecruitingObservational study
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Active, not recruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniel M Couriel, MD principal investigator

University of Michigan Rogel Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Alive at 1 Year After Transplant (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00763490, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2016.