Chronic Granulomatous DiseasePhase 1/2NCT02282904

Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide

A Phase 1/2 study testing Sirolimus, Donor peripheral blood stem cells. and Cyclophosphamide post transplant in people with Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) 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

Background: Chronic Granulomatous Disease (CGD) causes immune system problems. Treatment is usually a bone marrow transplant from a fully matched donor. Researchers want to try using partially matched donors for patients who do not have a fully matched donor available. Read more about this study

Who is it for?: Ages 2 to 65 years
Conditions the study is for: Chronic Granulomatous Disease
What is being tested?: Sirolimus, Donor peripheral blood stem cells. and Cyclophosphamide post transplant
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 23 Oct 2014to 10 Dec 2019
Phase: Phase 1/2
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 2 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Must have sufficient complications from underlying disease to warrant undergoing transplantation
Ages 2 years - 65 years
No appropriate HLA matched donor (available donor has greater than 1 mismatch or the single mismatch is not at DQ for unrelated donors (including cord blood products), or no available 6 out of 6 HLA matched related donor), or patients who may have an unrelated donor, but whose clinical status is such that the time required to obtain an unrelated donor would be life threatening.
HLA haploidentical family donor graft available.
Ability to comprehend and willingness to sign the informed consent or have a parent/guardian consent if the donor is a minor; assent being obtained from minors as appropriate
Must be HIV negative

Show all 10Show fewer

Must not be pregnant (confirmed by a negative serum beta-human chorionic gonadotropin (Beta-hCG) for women of child-bearing potential) or breastfeeding
Must be able to stay within one hour s travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post-transplant period.
Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance to NIH Form-200 NIH Durable Power of Attorney for Health Care Decision Making.
Where appropriate, subjects must agree to use contraception for 3 months post-transplant

Who cannot join

Major anticipated illness or organ failure incompatible with survival from Allo-transplant
Inadequate collection from prospective donors.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Post-Transplant Cyclophosphamide

Background:

Chronic Granulomatous Disease (CGD) causes immune system problems. Treatment is usually a bone marrow transplant from a fully matched donor. Researchers want to try using partially matched donors for patients who do not have a fully matched donor available. The researchers will also use the drug cyclophosphamide to try to improve the outcomes when using a partially matched donor.

Objective:

To learn the effectiveness of using cyclophosphamide with a transplant from a partially matched donor in treating CGD.

Eligibility:

Recipients: age 2-65 with CGD with an ongoing infection that has not been cured by standard treatment and no fully matched donor available in an appropriate timeframe.

Design:

Recipients will:
be admitted to the hospital 2 weeks before transplant.
be screened with blood and urine tests, breathing and heart health tests, X-rays, and/or magnetic resonance imaging. They may have a bone marrow aspiration and biopsy.
meet with a social worker and dentist.
get chemotherapy, radiation, and other medicines.
get an intravenous (IV) catheter in their chest.
have the transplant.
get more medicines and standard supportive care.
have blood drawn frequently.
have to stay in the Washington, D.C. area for 3 months post-transplant.
be followed closely for the first 6 months, and then less frequently for at least 5 years.

Read the detailed description

Allogeneic transplant using HLA matched donors, both related and unrelated, has proven curative for patients with various immunodeficiencies, including those with ongoing infections. However donor availability remains a limiting factor in the application of this treatment modality. The use of haploidentical donors has in the past been fraught with a greater rate of complications related to both higher rates of GvHD and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a subablative conditioning regimen followed by post-transplant cyclophosphamide for patients with CGD who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality.

Conditions: Chronic Granulomatous Disease
Being tested: Sirolimus, Donor peripheral blood stem cells., Cyclophosphamide post transplant, Total body 200cGy, Cyclophosphamide
Keywords: Chronic Granulomatous Disease, Halo-Identical Protocol, Transplant
Medical subject headings: Granulomatous Disease, Chronic

What participants receive

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

SirolimusDrug
Also called Rapamycin
For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).
Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).
Donor peripheral blood stem cells.Biological
Infuse donor graft.
Cyclophosphamide post transplantDrug
Also called Cytoxan post transplant
50 mg/kg/d IV infused over 90 minutes. Day +3 and +4
Total body 200cGyRadiation
Day -1
CyclophosphamideDrug
Also called Cytoxan
14.5 mg/kg IV over one hour Day -6 and -5
FludarabineDrug
Also called Fludara
30 mg/m2 over 30 minutes Day -6 through Day -2
BusulfanDrug
Also called Busulfex
Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Study groups in NCT02282904
Study group	Role	What they receive
CGD Recipient	Experimental	CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described Receives: Drug: Sirolimus; Biological: Donor peripheral blood stem cells.; Drug: Cyclophosphamide post transplant; Radiation: Total body 200cGy; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Busulfan

What is being measured

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

To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD
Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up
Measured: 5 years

Secondary outcomes (1)

To Determine the Safety of This Allogeneic HSCT Approach in Patients With CGD Including Transplant Related Toxicity, the Incidence of Acute and Chronic Graft-versus-host Disease, Immune Reconstitution, Overalland Disease-free Survival.
1. Stable chimerism as indicated by 30-50% myeloid engraftment and 50% lymphoid engraftment as assessed by 1 year post transplant. 2. Immune reconstitution levels with DHR as a marker of normal neutrophil function by 1 year post transplant. 3. GvHD grades of less than 3.
Measured: 1 year post transplant

Timeline

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

23 Oct 201410 Dec 2019

First posted5 Nov 2014 (estimated)
Study start23 Oct 2014
Primary completion10 Apr 2019
Study completion10 Dec 2019

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 Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02282904
Sponsor's protocol ID: 150007
Other IDs: 15-I-0007
Status last verified: 10 Dec 2019
First submitted: 4 Nov 2014
Last updated: 12 May 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolanos-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.
PubMed 18489989
Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011 Dec 1;118(23):6006-17. doi: 10.1182/blood-2011-07-338822. Epub 2011 Sep 14.
PubMed 21921045
Munchel A, Kesserwan C, Symons HJ, Luznik L, Kasamon YL, Jones RJ, Fuchs EJ. Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. Pediatr Rep. 2011 Jun 22;3 Suppl 2(Suppl 2):e15. doi: 10.4081/pr.2011.s2.e15.
PubMed 22053277

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 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Post-Transplant Cyclophosphamide
ClinicalTrials.gov ID: NCT02282904
Acronym / sponsor ID: 150007
Conditions: Chronic Granulomatous Disease
Keywords: Chronic Granulomatous Disease, Halo-Identical Protocol, Transplant
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 7 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: 23 Oct 2014
Primary completion: 10 Apr 2019 (actual)
Study completion: 10 Dec 2019 (actual)
First posted: 5 Nov 2014 (estimated)
Results: Posted 1 May 2020

Clinical summary

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

Background:

Chronic Granulomatous Disease (CGD) causes immune system problems. Treatment is usually a bone marrow transplant from a fully matched donor. Researchers want to try using partially matched donors for patients who do not have a fully matched donor available. The researchers will also use the drug cyclophosphamide to try to improve the outcomes when using a partially matched donor.

Objective:

To learn the effectiveness of using cyclophosphamide with a transplant from a partially matched donor in treating CGD.

Eligibility:

Recipients: age 2-65 with CGD with an ongoing infection that has not been cured by standard treatment and no fully matched donor available in an appropriate timeframe.

Design:

Recipients will:
be admitted to the hospital 2 weeks before transplant.
be screened with blood and urine tests, breathing and heart health tests, X-rays, and/or magnetic resonance imaging. They may have a bone marrow aspiration and biopsy.
meet with a social worker and dentist.
get chemotherapy, radiation, and other medicines.
get an intravenous (IV) catheter in their chest.
have the transplant.
get more medicines and standard supportive care.
have blood drawn frequently.
have to stay in the Washington, D.C. area for 3 months post-transplant.
be followed closely for the first 6 months, and then less frequently for at least 5 years.

Detailed description

Study design

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

Arm	Type	Receives
CGD Recipient	Experimental	Drug: Sirolimus, Biological: Donor peripheral blood stem cells., Drug: Cyclophosphamide post transplant, Radiation: Total body 200cGy, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: BusulfanCGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Who may qualify

Ages: 2 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (10 listed)

Must have sufficient complications from underlying disease to warrant undergoing transplantation
Ages 2 years - 65 years
No appropriate HLA matched donor (available donor has greater than 1 mismatch or the single mismatch is not at DQ for unrelated donors (including cord blood products), or no available 6 out of 6 HLA matched related donor), or patients who may have an unrelated donor, but whose clinical status is such that the time required to obtain an unrelated donor would be life threatening.
HLA haploidentical family donor graft available.
Ability to comprehend and willingness to sign the informed consent or have a parent/guardian consent if the donor is a minor; assent being obtained from minors as appropriate

Key exclusion criteria (2 listed)

Major anticipated illness or organ failure incompatible with survival from Allo-transplant
Inadequate collection from prospective donors.

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: RapamycinFor pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD). Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).	Drug	CGD Recipient
Donor peripheral blood stem cells.Infuse donor graft.	Biological	CGD Recipient
Cyclophosphamide post transplantAlso: Cytoxan post transplant50 mg/kg/d IV infused over 90 minutes. Day +3 and +4	Drug	CGD Recipient
Total body 200cGyDay -1	Radiation	CGD Recipient
CyclophosphamideAlso: Cytoxan14.5 mg/kg IV over one hour Day -6 and -5	Drug	CGD Recipient
FludarabineAlso: Fludara30 mg/m2 over 30 minutes Day -6 through Day -2	Drug	CGD Recipient
BusulfanAlso: BusulfexBusulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2	Drug	CGD Recipient

Primary outcome

To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD
Time frame: 5 years
Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up

1 secondary outcome

To Determine the Safety of This Allogeneic HSCT Approach in Patients With CGD Including Transplant Related Toxicity, the Incidence of Acute and Chronic Graft-versus-host Disease, Immune Reconstitution, Overalland Disease-free Survival.
Time frame: 1 year post transplant

Results and safety

Results posted to the registry on 1 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CGD Recipient	7	7

Primary outcome: To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD

Time frame: 5 years. Count of participants. Unit: Participants

Measure	CGD Recipient n = 7
Greater than 20% donor chimerism	7
Resolution of inflammation or infection	7

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse Events were collected over 5 years (2015 to 2019). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CGD Recipient	3 of 7 (42.9%)	7 of 7 (100%)	2 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18489989Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolanos-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.
Background: PubMed 21921045Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011 Dec 1;118(23):6006-17. doi: 10.1182/blood-2011-07-338822. Epub 2011 Sep 14.
Background: PubMed 22053277Munchel A, Kesserwan C, Symons HJ, Luznik L, Kasamon YL, Jones RJ, Fuchs EJ. Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. Pediatr Rep. 2011 Jun 22;3 Suppl 2(Suppl 2):e15. doi: 10.4081/pr.2011.s2.e15.
Individual participant dataSharing planned: No

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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.

Elizabeth M Kang, M.D. principal investigator

National Institute of Allergy and Infectious Diseases (NIAID)

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 2 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 12 May 2020. 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 combined 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.

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 1 May 2020). 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?

To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD (time frame: 5 years). 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 NCT02282904, 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 12 May 2020.