Severe Combined ImmunodeficiencyPhase 2NCT01182675

Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim

A Phase 2 study testing Transplant Conditioning with Mobilization Only and Transplant Conditioning with Mobilization and Alemtuzumab in people with Severe Combined Immunodeficiency, run by University of California, San Francisco at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 3 years
Conditions the study is for: Severe Combined Immunodeficiency
What is being tested?: Transplant Conditioning with Mobilization Only and Transplant Conditioning with Mobilization and Alemtuzumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: Aug 2010to Sep 2013
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 3 years
All sexes
No healthy volunteers
Child

Who may be able to join

Patients with classic SCID phenotype (<400 CD3/ul or maternally engrafted and <10% of normal PHA lymphoproliferative response). Genotypic identification is preferable, but not required.
Patients must have an acceptable stem cell donor (HLA matched relative, 9 or 10/10 HLA-matched unrelated, or haplocompatible relative).

Who cannot join

Patients with "leaky" SCID syndromes, Omenn's Syndrome, reticular dysgenesis, ADA deficiency
Lansky score <60%
Patient with expected survival <4 weeks (including disseminated CMV infection involving lungs and/or CNS)

Trial locations and contacts

1 site in 1 country.

United States1 site

UCSF Benioff Children's Hospital
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim

The goal of this study is to develop a novel approach to hematopoietic stem cell transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune reconstitution. Rather than classic chemotherapeutic agents, the investigators will utilize a targeted stem cell mobilizer, plerixafor, in combination with alemtuzumab, a monoclonal antibody. Correlative scientific questions will include: 1) efficacy and characteristics of host stem cell mobilization; and 2) alemtuzumab pharmacokinetics in very young children.

Read the detailed description

The goal of this study is to develop an approach to hematopoietic stem cell transplantation for children with Severe Combined Immunodeficiency Disease (SCID) that eliminates the use of toxic chemotherapy conditioning and maximizes the likelihood of T and B cell immune reconstitution. SCID is a rare primary immunodeficiency disease in which there are multiple genotypes and phenotypes, and depending on various factors including the presence of B cell and NK cells, and the presence of maternal cells in the patient's circulation, there are numerous ways to approach a transplant. The major issues that must be addressed in any approach to transplantation for SCID are graft rejection and T and B cell immune reconstitution. Depending on the specific SCID diagnosis, the phenotype, and the presence of maternal engraftment at diagnosis, we will evaluate two transplant approaches that will attempt to optimize the engraftment of donor HSC and the likelihood of T and B cell reconstitution while eliminating the use of toxic chemotherapy conditioning.

Primary Objective: To determine if the administration of plerixafor \& filgrastim (G-CSF) prior to stem cell infusion results in increased donor stem cell occupancy of available bone marrow niches and B-cell engraftment in patients with SCID.
Secondary Objectives:
To determine if NK cell depletion with Alemtuzumab will overcome NK-mediated graft resistance in haplocompatible transplants for NK+ SCID. ii. To determine the optimal dosing of Alemtuzumab in very young children. iii. To determine the immunophenotypic characteristics of CD34+ cells mobilized and engrafted in patients receiving plerixafor \& filgrastim prior to HCT. iv. To determine the thymic output, as measured by T-cell receptor excision circles, in patients receiving haplocompatible transplants \& boosts.

Conditions: Severe Combined Immunodeficiency
Being tested: Transplant Conditioning with Mobilization Only, Transplant Conditioning with Mobilization and Alemtuzumab
Keywords: SCID, Transplant, Alemtuzumab, Plerixafor
Medical subject headings: Severe Combined Immunodeficiency

What participants receive

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

Transplant Conditioning with Mobilization OnlyDrug
Also called Conditioning with Filgrastim and Plerixafor
Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0 Transplant
Transplant Conditioning with Mobilization and AlemtuzumabDrug
Also called Conditioning with Filgrastim, Plerixafor, and Alemtuzumab
Day -7: Alemtuzumab 0.3 mg test dose then 0.3 mg/kg IV; Day -6: Alemtuzumab 0.3 mg/kg IV; Day -5: Alemtuzumab 0.3 mg/kg IV; Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0: Transplant

Study groups in NCT01182675
Study group	Role	What they receive
T-cell Graft Permissive SCID	Experimental	Patients with SCID with: i. NK- phenotype; ii. NK+ phenotype with 10/10 HLA-matched relative or unrelated donor; or iii. NK+ phenotype with maternal engraftment by STR analysis and undergoing haplocompatible HSCT from maternal donor Intervention: Transplant Conditioning with Mobilization Only Receives: Drug: Transplant Conditioning with Mobilization Only
T-cell Graft Resistant SCID	Experimental	Patients with SCID with NK+ phenotype with HLA-mismatched donor Intervention: Transplant Conditioning with Mobilization and Alemtuzumab Receives: Drug: Transplant Conditioning with Mobilization and Alemtuzumab

What is being measured

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

Engraftment of Donor B-cells in Blood by STR Testing
Number of participants in whom donor B cells were detected in the patient's blood after HSCT.
Measured: 1 Year

Secondary outcomes (5)

Incidence of Acute GVHD
Measured: 100 Days
Incidence of Chronic GVHD
Measured: 2 Years
Percentage of Patients Who Become Independent From Regular IVIG Infusion
Based on B-cell function assays from the patient's blood, we will be able to determine if patients are able to successfully discontinue IVIG infusions.
Measured: 2 Years
Number of Patients With Engraftment of Donor Stem Cells in Bone Marrow by STR Testing
We will measure whether we are able to detect donor stem cells in the patient's bone marrow after HSCT.
Measured: 1 Year
Number of Patients Who Achieve Engraftment of Donor T-cells in Blood by STR Testing
We will measure whether we are able to detect donor T-cells in the patient's blood after HSCT.
Measured: 1 Year

Timeline

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

Aug 2010Sep 2013

First posted17 Aug 2010 (estimated)
Study startAug 2010
Primary completionSep 2013
Study completionSep 2013

Why it stopped: Insufficient evidence of efficacy

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 (3)Papers the sponsor has linked to this study.
Other trials for Severe Combined ImmunodeficiencyStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01182675
Sponsor's protocol ID: UCSF10-00701
Status last verified: Jul 2018
First submitted: 9 Aug 2010
Last updated: 31 Jul 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ. Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation. Biol Blood Marrow Transplant. 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008.
PubMed 18804042
Dvorak CC, Cowan MJ. Radiosensitive severe combined immunodeficiency disease. Immunol Allergy Clin North Am. 2010 Feb;30(1):125-42. doi: 10.1016/j.iac.2009.10.004.
PubMed 20113890
Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant. 2008 Jan;41(2):119-26. doi: 10.1038/sj.bmt.1705890. Epub 2007 Oct 29.
PubMed 17968328

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

RecruitingPhase 1/2
Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
X-linked Severe Combined Immunodeficiency (XSCID)
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
Not yet recruitingPhase 1/2
SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection
SCID, X-Linked
Not yet recruiting
Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8

All Severe Combined Immunodeficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Hematopoietic Stem Cell Transplantation for Children With Severe Combined Immunodeficiency Disease Utilizing Alemtuzumab and Mobilization With Plerixafor & Filgrastim
ClinicalTrials.gov ID: NCT01182675
Acronym / sponsor ID: UCSF10-00701
Conditions: Severe Combined Immunodeficiency
Keywords: SCID, Transplant, Alemtuzumab, Plerixafor
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Insufficient evidence of efficacy
Enrolment: 7 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Study start: Aug 2010
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 17 Aug 2010 (estimated)
Results: Posted 10 Nov 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

Primary Objective: To determine if the administration of plerixafor \& filgrastim (G-CSF) prior to stem cell infusion results in increased donor stem cell occupancy of available bone marrow niches and B-cell engraftment in patients with SCID.
Secondary Objectives:
To determine if NK cell depletion with Alemtuzumab will overcome NK-mediated graft resistance in haplocompatible transplants for NK+ SCID. ii. To determine the optimal dosing of Alemtuzumab in very young children. iii. To determine the immunophenotypic characteristics of CD34+ cells mobilized and engrafted in patients receiving plerixafor \& filgrastim prior to HCT. iv. To determine the thymic output, as measured by T-cell receptor excision circles, in patients receiving haplocompatible transplants \& boosts.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
T-cell Graft Permissive SCID	Experimental	Drug: Transplant Conditioning with Mobilization OnlyPatients with SCID with: i. NK- phenotype; ii. NK+ phenotype with 10/10 HLA-matched relative or unrelated donor; or iii. NK+ phenotype with maternal engraftment by STR analysis and undergoing haplocompatible HSCT from maternal donor Intervention: Transplant Conditioning with Mobilization Only
T-cell Graft Resistant SCID	Experimental	Drug: Transplant Conditioning with Mobilization and AlemtuzumabPatients with SCID with NK+ phenotype with HLA-mismatched donor Intervention: Transplant Conditioning with Mobilization and Alemtuzumab

Who may qualify

Ages: Up to 3 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

Patients with classic SCID phenotype (<400 CD3/ul or maternally engrafted and <10% of normal PHA lymphoproliferative response). Genotypic identification is preferable, but not required.
Patients must have an acceptable stem cell donor (HLA matched relative, 9 or 10/10 HLA-matched unrelated, or haplocompatible relative).

Key exclusion criteria (3 listed)

Patients with "leaky" SCID syndromes, Omenn's Syndrome, reticular dysgenesis, ADA deficiency
Lansky score <60%
Patient with expected survival <4 weeks (including disseminated CMV infection involving lungs and/or CNS)

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
Transplant Conditioning with Mobilization OnlyAlso: Conditioning with Filgrastim and PlerixaforDay -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0 Transplant	Drug	T-cell Graft Permissive SCID
Transplant Conditioning with Mobilization and AlemtuzumabAlso: Conditioning with Filgrastim, Plerixafor, and AlemtuzumabDay -7: Alemtuzumab 0.3 mg test dose then 0.3 mg/kg IV; Day -6: Alemtuzumab 0.3 mg/kg IV; Day -5: Alemtuzumab 0.3 mg/kg IV; Day -4: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -3: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -2: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day -1: Filgrastim (G-CSF) 5 mcg/kg IV q12 hours; Day 0: Plerixafor 240 mcg/kg subcutaneous 9-12 hours prior to transplant; Day 0: Transplant	Drug	T-cell Graft Resistant SCID

Primary outcome

Engraftment of Donor B-cells in Blood by STR Testing
Time frame: 1 Year
Number of participants in whom donor B cells were detected in the patient's blood after HSCT.

5 secondary outcomes

Incidence of Acute GVHD
Time frame: 100 Days
Incidence of Chronic GVHD
Time frame: 2 Years
Percentage of Patients Who Become Independent From Regular IVIG Infusion
Time frame: 2 Years
Number of Patients With Engraftment of Donor Stem Cells in Bone Marrow by STR Testing
Time frame: 1 Year
Number of Patients Who Achieve Engraftment of Donor T-cells in Blood by STR Testing
Time frame: 1 Year

Results and safety

Results posted to the registry on 10 Nov 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
T-cell Graft Permissive SCID	7	7
T-cell Graft Resistant SCID	0	0

Primary outcome: Engraftment of Donor B-cells in Blood by STR Testing

Time frame: 1 Year. Number. Unit: participants

Measure	T-cell Graft Permissive SCID n = 7	T-cell Graft Resistant SCID n = 0
Value	0	–

Population analysed: No patients with T-cell Graft Resistant SCID were enrolled during the time the trial was open.

5 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
T-cell Graft Permissive SCID	0 of 7 (0%)	0 of 7 (0%)	0 of 7
T-cell Graft Resistant SCID	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18804042Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ. Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation. Biol Blood Marrow Transplant. 2008 Oct;14(10):1125-1133. doi: 10.1016/j.bbmt.2008.07.008.
Background: PubMed 20113890Dvorak CC, Cowan MJ. Radiosensitive severe combined immunodeficiency disease. Immunol Allergy Clin North Am. 2010 Feb;30(1):125-42. doi: 10.1016/j.iac.2009.10.004.
Background: PubMed 17968328Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant. 2008 Jan;41(2):119-26. doi: 10.1038/sj.bmt.1705890. Epub 2007 Oct 29.

Related trials for Severe Combined Immunodeficiency

RecruitingPhase 1/2
Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
X-linked Severe Combined Immunodeficiency (XSCID)
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
Not yet recruitingPhase 1/2
SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection
SCID, X-Linked
Not yet recruiting
Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8

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.

Christopher C Dvorak, M.D. principal investigator

University of California, San Francisco

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 2 inclusion and 3 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: stopped early, as of the sponsor's last update on 31 Jul 2018. 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 10 Nov 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?

Engraftment of Donor B-cells in Blood by STR Testing (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 NCT01182675, which also lists 3 linked publications.

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 31 Jul 2018.