Severe Combined ImmunodeficiencyPhase 2NCT02177760

Sirolimus Prophylaxis for aGVHD in TME SCID

A Phase 2 study testing Sirolimus in people with Severe Combined Immunodeficiency and Transplacental Maternal Engraftment, run by University of California, San Francisco at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

Search all trials

Trial summary

Who is it for?: Ages 1 day to 1 year
Conditions the study is for: Severe Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell Transplant
What is being tested?: Sirolimus
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Jul 2014to Nov 2015
Phase: Phase 2
Are there results?: None posted in the registry

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 1 day to 1 year
All sexes
No healthy volunteers
Child

Who may be able to join

Infants diagnosed with SCID on CA newborn screen
Evidence of Maternal Engraftment
Unconditioned haploidentical hematopoeitic stem cell transplant

Who cannot join

Evidence of acute graft vs. host disease

Trial locations and contacts

1 site in 1 country.

United States1 site

Benioff Children's Hospital at UCSF Medical Center
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT)

Study Design: SCID infants receiving an unconditioned haploidentical transplant will be started on Sirolimus (0.05 mg/kg/day) day -5 for Acute Graft-Versus-Host Disease (aGVHD) prophylaxis. Sirolimus levels will be monitored with goal sirolimus trough level of 5-8 ng/mL. Patients will be monitored for signs of aGVHD as defined by UCSF SOP CL 221.06 through day +100. Sirolimus will be tapered once T-regulatory cell to CD4 effector cell ratio is > or = 9%.

Setting: Inpatient BMT Unit Benioff Children's Hospital at UCSF Medical Center

Study Subjects: 15 infants with diagnosis of maternally engrafted T cells SCID by CA Newborn screen receiving unconditioned haploidentical HSCT

Main Outcome Measures: Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by SOP CL 221.06 by Day +100.

Hypothesis 1. Patients placed on sirolimus prophylaxis will have lower incidence of aGVHD compared to historical controls.

Hypothesis 2. Lower doses of sirolimus milligram per kilogram will be required to maintain goal troughs of 5-8 ng/mL.

Conditions: Severe Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell Transplant
Being tested: Sirolimus
Keywords: SCID, severe combined immunodeficiency, maternal engraftment, aGVHD prophylaxis, sirolimus
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.

SirolimusDrug
Also called Rapamune

Study groups in NCT02177760
Study group	Role	What they receive
Sirolimus	Experimental	Sirolimus (0.05 mg/kg/day) day -5 for aGVHD prophylaxis through day +100 or until T-regulatory cells >9% of CD4 effector cells; whichever comes first. Receives: Drug: Sirolimus

What is being measured

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

Incidence of aGVHD
Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by UCSF SOP CL 221.06 by Day +100.
Measured: 105 days

Secondary outcomes (2)

T-regulatory cell enumeration
T-regulatory cell enumeration studies by blood draw prior to prophylaxis and at day +30, day+60, day+100.
Measured: 105 days
Sirolimus therapeutic drug monitoring
Sirolimus therapeutic drug monitoring will be done via blood draws(after initial 4th dose; thereafter every 4th dose with adjustment; once stable it will be measured weekly). We will determine the average dose in milligrams per kilograms that would be needed to reach therapeutic trough levels of 5-8 ng/mL.
Measured: 105 days

Timeline

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

Jul 2014Nov 2015

First posted30 Jun 2014 (estimated)
Study startJul 2014
Primary completionNov 2015
Study completionNov 2015

Why it stopped: Preliminary data suggested a better approach available

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (9)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: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02177760
Sponsor's protocol ID: 14-13024
Status last verified: Dec 2015
First submitted: 19 Jun 2014
Last updated: 3 Dec 2015
Results posted: No
Data monitoring committee: Yes

Publications

Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, Myers LA, Ward FE. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999 Feb 18;340(7):508-16. doi: 10.1056/NEJM199902183400703.
PubMed 10021471
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
Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001 Sep 15;98(6):1847-51. doi: 10.1182/blood.v98.6.1847.
PubMed 11535520
Pulsipher MA, Wall DA, Grimley M, Goyal RK, Boucher KM, Hankins P, Grupp SA, Bunin N. A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL). Br J Haematol. 2009 Dec;147(5):691-9. doi: 10.1111/j.1365-2141.2009.07889.x. Epub 2009 Sep 10.
PubMed 19744131
Cutler C, Antin JH. Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update. Curr Opin Hematol. 2010 Nov;17(6):500-4. doi: 10.1097/MOH.0b013e32833e5b2e.
PubMed 20717025
Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll WL, Raetz E, Gardner S, Gastier-Foster JM, Howrie D, Goyal RK, Douglas JG, Borowitz M, Barnes Y, Teachey DT, Taylor C, Grupp SA. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood. 2014 Mar 27;123(13):2017-25. doi: 10.1182/blood-2013-10-534297. Epub 2014 Feb 4.
PubMed 24497539
Yong PL, Russo P, Sullivan KE. Use of sirolimus in IPEX and IPEX-like children. J Clin Immunol. 2008 Sep;28(5):581-7. doi: 10.1007/s10875-008-9196-1. Epub 2008 May 15.
PubMed 18481161
Strauss L, Czystowska M, Szajnik M, Mandapathil M, Whiteside TL. Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One. 2009 Jun 22;4(6):e5994. doi: 10.1371/journal.pone.0005994.
PubMed 19543393
Fujioka T, Tamaki H, Ikegame K, Yoshihara S, Taniguchi K, Kaida K, Kato R, Inoue T, Nakata J, Ishii S, Soma T, Okada M, Ogawa H. Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA-mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD. Bone Marrow Transplant. 2013 Jun;48(6):859-64. doi: 10.1038/bmt.2012.232. Epub 2012 Nov 19.
PubMed 23165499

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

Not yet recruiting
Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8
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)
Active, not recruitingPhase 2
Conditioning SCID Infants Diagnosed Early
SCID

All Severe Combined Immunodeficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT)
ClinicalTrials.gov ID: NCT02177760
Acronym / sponsor ID: 14-13024
Conditions: Severe Combined Immunodeficiency, Transplacental Maternal Engraftment, Stem Cell Transplant
Keywords: SCID, severe combined immunodeficiency, maternal engraftment, aGVHD prophylaxis, sirolimus
Phase: Phase 2
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Preliminary data suggested a better approach available
Enrolment: 0 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Study start: Jul 2014
Primary completion: Nov 2015 (actual)
Study completion: Nov 2015 (actual)
First posted: 30 Jun 2014 (estimated)
Results: Not posted in the source record

Clinical summary

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

Setting: Inpatient BMT Unit Benioff Children's Hospital at UCSF Medical Center

Study Subjects: 15 infants with diagnosis of maternally engrafted T cells SCID by CA Newborn screen receiving unconditioned haploidentical HSCT

Main Outcome Measures: Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by SOP CL 221.06 by Day +100.

Hypothesis 1. Patients placed on sirolimus prophylaxis will have lower incidence of aGVHD compared to historical controls.

Hypothesis 2. Lower doses of sirolimus milligram per kilogram will be required to maintain goal troughs of 5-8 ng/mL.

Study design

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

Arm	Type	Receives
Sirolimus	Experimental	Drug: SirolimusSirolimus (0.05 mg/kg/day) day -5 for aGVHD prophylaxis through day +100 or until T-regulatory cells >9% of CD4 effector cells; whichever comes first.

Who may qualify

Ages: 1 day to 1 year
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Infants diagnosed with SCID on CA newborn screen
Evidence of Maternal Engraftment
Unconditioned haploidentical hematopoeitic stem cell transplant

Key exclusion criteria (1 listed)

Evidence of acute graft vs. host disease

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
SirolimusAlso: Rapamune	Drug	Sirolimus

Primary outcome

Incidence of aGVHD
Time frame: 105 days
Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by UCSF SOP CL 221.06 by Day +100.

2 secondary outcomes

T-regulatory cell enumeration
Time frame: 105 days
Sirolimus therapeutic drug monitoring
Time frame: 105 days

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
Background: PubMed 10021471Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, Myers LA, Ward FE. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999 Feb 18;340(7):508-16. doi: 10.1056/NEJM199902183400703.
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.
Background: PubMed 11535520Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001 Sep 15;98(6):1847-51. doi: 10.1182/blood.v98.6.1847.
Background: PubMed 19744131Pulsipher MA, Wall DA, Grimley M, Goyal RK, Boucher KM, Hankins P, Grupp SA, Bunin N. A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL). Br J Haematol. 2009 Dec;147(5):691-9. doi: 10.1111/j.1365-2141.2009.07889.x. Epub 2009 Sep 10.
Background: PubMed 20717025Cutler C, Antin JH. Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update. Curr Opin Hematol. 2010 Nov;17(6):500-4. doi: 10.1097/MOH.0b013e32833e5b2e.
Background: PubMed 24497539Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll WL, Raetz E, Gardner S, Gastier-Foster JM, Howrie D, Goyal RK, Douglas JG, Borowitz M, Barnes Y, Teachey DT, Taylor C, Grupp SA. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood. 2014 Mar 27;123(13):2017-25. doi: 10.1182/blood-2013-10-534297. Epub 2014 Feb 4.
Background: PubMed 18481161Yong PL, Russo P, Sullivan KE. Use of sirolimus in IPEX and IPEX-like children. J Clin Immunol. 2008 Sep;28(5):581-7. doi: 10.1007/s10875-008-9196-1. Epub 2008 May 15.
Background: PubMed 19543393Strauss L, Czystowska M, Szajnik M, Mandapathil M, Whiteside TL. Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One. 2009 Jun 22;4(6):e5994. doi: 10.1371/journal.pone.0005994.
Background: PubMed 23165499Fujioka T, Tamaki H, Ikegame K, Yoshihara S, Taniguchi K, Kaida K, Kato R, Inoue T, Nakata J, Ishii S, Soma T, Okada M, Ogawa H. Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA-mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD. Bone Marrow Transplant. 2013 Jun;48(6):859-64. doi: 10.1038/bmt.2012.232. Epub 2012 Nov 19.

Related trials for Severe Combined Immunodeficiency

Not yet recruiting
Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8
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)
Active, not recruitingPhase 2
Conditioning SCID Infants Diagnosed Early
SCID

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.

Chris Dvorak, MD 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?

A Phase 2 study testing Sirolimus in people with Severe Combined Immunodeficiency and Transplacental Maternal Engraftment, run by University of California, San Francisco at 1 site in United States.

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 3 inclusion and 1 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: withdrawn, as of the sponsor's last update on 3 Dec 2015. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Incidence of aGVHD (time frame: 105 days). 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 NCT02177760, which also lists 9 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 3 Dec 2015.