Non Malignant DisordersPhase 1NCT00744692

Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

A Phase 1 study testing Unrelated Umbilical Cord Blood Transplant and Reduced Intensity Conditioning in people with Non Malignant Disorders and Immunodeficiencies, run by Duke University 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

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders. Read more about this study

Who is it for?: Ages Up to 21 years
Conditions the study is for: Non Malignant Disorders, Immunodeficiencies, Congenital Marrow Failures
What is being tested?: Unrelated Umbilical Cord Blood Transplant and Reduced Intensity Conditioning
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 22 participants
Where: 1 siteUnited States
Study dates: Oct 2008to Apr 2014
Phase: Phase 1
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 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
Performance score (lansky or karnofsky) greater than or equal to 70
Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
Informed consent
Not pregnant or breast feeding

Show all 10Show fewer

Minimum life expectancy of at least 6 months
HIV negative
No uncontrolled infections at the time of cytoreduction
Disease specific inclusion criteria

Who cannot join

Patients with hemoglobinopathies > 3 years of age
UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
Available HLA-matched related living donor able to donate without previous UCB donation
Allogeneic hematopoietic stem cell transplant within the previous 6 months
Any active malignancy, MDS, or any history of malignancy
Severe acquired aplastic anemia

Show all 11Show fewer

DLCO < 60% of normal value for age; requirement for supplemental oxygen
Uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms)
Pregnancy or nursing mother
HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR
Any condition that precludes serial follow-up

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke University Medical Center Pediatric Blood and Marrow Transplant Program
Durham, North Carolina, 27705

Other trials in United States

About this study

Official title: A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation

Read the detailed description

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The secondary objectives are:

To describe the pace of neutrophil and platelet recovery
To evaluate the pace of immune reconstitution.
To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
To describe the incidence of grade 3-4 organ toxicity
To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
To evaluate the incidence of late graft failures at 2 years post-transplant

Conditions: Non Malignant Disorders, Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, Sickle Cell
Being tested: Unrelated Umbilical Cord Blood Transplant, Reduced Intensity Conditioning
Keywords: Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, SCIDS, Wiskott Aldrich, FEL, HLH, IPEX, LAD, Sickle Cell, Thalassemia, Omenn's Syndrome, Hurler's Syndrome, MLD, ALD, Sanfilippo, Krabbe, Hunter's syndrome, TaySachs
Medical subject headings: Immunologic Deficiency Syndromes, Hemoglobinopathies, Metabolism, Inborn Errors, Thalassemia, Lysosomal Storage Diseases, Severe Combined Immunodeficiency, Mucopolysaccharidosis I, Mucopolysaccharidosis II

What participants receive

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

Unrelated Umbilical Cord Blood TransplantBiological
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant
Reduced Intensity ConditioningDrug
Also called Campath, Hydroxyurea, Fludarabine, Melphalan

Study groups in NCT00744692
Study group	Role	What they receive
RIC Cord Blood Transplant	Experimental	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant Receives: Biological: Unrelated Umbilical Cord Blood Transplant; Drug: Reduced Intensity Conditioning

What is being measured

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

Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.
Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders.
Measured: 180 days post transplant

Secondary outcomes (8)

To Describe the Pace of Neutrophil Recovery
Neutrophil recovery was defined as the first day of an absolute neutrophil count (ANC) more than 500/uL for 3 consecutive days not secondary to granulocyte infusions
Measured: 42 days post transplant
To Evaluate the Pace of Immune Reconstitution.
Immune reconstitution after RIC in UCBT was described. CD4 count is a standard measure of immune reconstitution and is described here. Additional data is available upon request.
Measured: 1 year post transplant
To Determine the Overall Survival at day180 Post-transplant
To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis
Measured: 180 days
To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis
Measured: 100 days post transplant
To Describe the Incidence of Grade 3-4 Organ Toxicity
Measured: 2 years post transplant
To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure
Measured: at least 2 years post transplant
To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant
Measured: 2 years post transplant
To Describe the Pace of Platelet Recovery
Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions
Measured: 180 days post transplant

Timeline

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

Oct 2008Apr 2014

First posted1 Sep 2008 (estimated)
Study startOct 2008
Primary completionDec 2012
Study completionApr 2014

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 Non Malignant DisordersStudies of the same condition, open and under way.
More trials run by Duke UniversityThe 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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00744692
Sponsor's protocol ID: Pro00008753
Status last verified: Jul 2014
First submitted: 28 Aug 2008
Last updated: 13 Aug 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A, Hale G, Driscoll TA, Martin PL, Page KM, Flickinger K, Moffet J, Niedzwiecki D, Kurtzberg J, Szabolcs P. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.
PubMed 24296492

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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Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation
ClinicalTrials.gov ID: NCT00744692
Acronym / sponsor ID: Pro00008753
Conditions: Non Malignant Disorders, Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, Sickle Cell
Keywords: Immunodeficiencies, Congenital Marrow Failures, Hemoglobinopathies, Inborn Errors of Metabolism, SCIDS, Wiskott Aldrich, FEL, HLH
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Study start: Oct 2008
Primary completion: Dec 2012 (actual)
Study completion: Apr 2014 (actual)
First posted: 1 Sep 2008 (estimated)
Results: Posted 13 Aug 2014

Clinical summary

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

Detailed description

The secondary objectives are:

To describe the pace of neutrophil and platelet recovery
To evaluate the pace of immune reconstitution.
To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
To describe the incidence of grade 3-4 organ toxicity
To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
To evaluate the incidence of late graft failures at 2 years post-transplant

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
RIC Cord Blood Transplant	Experimental	Biological: Unrelated Umbilical Cord Blood Transplant, Drug: Reduced Intensity ConditioningReduced Intensity Conditioning for Umbilical Cord Blood Transplant

Who may qualify

Ages: Up to 21 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (10 listed)

0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
Performance score (lansky or karnofsky) greater than or equal to 70
Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
Informed consent

Key exclusion criteria (11 listed)

Patients with hemoglobinopathies > 3 years of age
UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
Available HLA-matched related living donor able to donate without previous UCB donation
Allogeneic hematopoietic stem cell transplant within the previous 6 months
Any active malignancy, MDS, or any history of malignancy

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
Unrelated Umbilical Cord Blood TransplantReduced Intensity Conditioning for unrelated umbilical cord blood transplant	Biological	RIC Cord Blood Transplant
Reduced Intensity ConditioningAlso: Campath, Hydroxyurea, Fludarabine, Melphalan	Drug	RIC Cord Blood Transplant

Primary outcome

Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.
Time frame: 180 days post transplant
Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders.

8 secondary outcomes

To Describe the Pace of Neutrophil Recovery
Time frame: 42 days post transplant
To Evaluate the Pace of Immune Reconstitution.
Time frame: 1 year post transplant
To Determine the Overall Survival at day180 Post-transplant
Time frame: 180 days
To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)
Time frame: 100 days post transplant
To Describe the Incidence of Grade 3-4 Organ Toxicity
Time frame: 2 years post transplant
To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure
Time frame: at least 2 years post transplant
To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant
Time frame: 2 years post transplant
To Describe the Pace of Platelet Recovery
Time frame: 180 days post transplant

Results and safety

Results posted to the registry on 13 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
RIC Cord Blood Transplant	22	22

Primary outcome: Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.

Time frame: 180 days post transplant. Number. Unit: % of participants

Measure	RIC Cord Blood Transplant n = 18
Value	88

Population analysed: Of the 22 patients enrolled, 18 patients were alive at 180 days, the time-point for primary end point

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
RIC Cord Blood Transplant	18 of 22 (81.8%)	0 of 22 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24296492Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A, Hale G, Driscoll TA, Martin PL, Page KM, Flickinger K, Moffet J, Niedzwiecki D, Kurtzberg J, Szabolcs P. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.

Related trials for Non Malignant Disorders

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Enrolling by invitationPhase 1
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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.

Suhag Parikh, MD principal investigator

Duke Pediatric Blood and Marrow Transplant

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 10 inclusion and 11 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 13 Aug 2014. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 13 Aug 2014). 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?

Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders. (time frame: 180 days post transplant). 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 NCT00744692, 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 13 Aug 2014.