Ignite Creation Date:
2025-12-25 @ 12:36 AM
Ignite Modification Date:
2026-04-23 @ 8:24 PM
Study NCT ID:
NCT02579967
Status:
RECRUITING
Last Update Posted:
2025-12-24
First Post:
2015-10-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Status:
RECRUITING
Status Verified Date:
2025-12-16
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems.
Objective:
To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies.
Eligibility:
Donors: Healthy people ages 4 or older
Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Participants will have urine tests, EKG, and chest x-ray.
Donors will have:
Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone.
OR
Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm.
Possible vein assessment or pre-anesthesia evaluation
Recipients will have:
Lung test, heart tests, radiology scans, CT scans, and dental exam
Possible tissue biopsies or lumbar puncture
Bone marrow and a small piece of bone removed by needle in the hipbone.
Chemotherapy 1-2 weeks before transplant day
Donor stem cell donation through a catheter put into a vein in the chest or neck
Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures.
After discharge, recipients will:
Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission.
Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years....
Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems.
Objective:
To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies.
Eligibility:
Donors: Healthy people ages 4 or older
Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Participants will have urine tests, EKG, and chest x-ray.
Donors will have:
Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone.
OR
Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm.
Possible vein assessment or pre-anesthesia evaluation
Recipients will have:
Lung test, heart tests, radiology scans, CT scans, and dental exam
Possible tissue biopsies or lumbar puncture
Bone marrow and a small piece of bone removed by needle in the hipbone.
Chemotherapy 1-2 weeks before transplant day
Donor stem cell donation through a catheter put into a vein in the chest or neck
Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures.
After discharge, recipients will:
Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission.
Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years....
Detailed Description:
Background:
* Primary immunodeficiency diseases (PIDs) are conditions associated with major quantitative or qualitative immunologic abnormalities that are, in most cases, due to defects in cells of hematopoietic origin
* Participants with PID can have life-threatening complications including malignancy, recurrent infection, and autoimmunity/immune dysregulation
* Allogeneic blood or marrow transplantation (allo BMT) has the potential to cure the immune defect in PID and thereby reduce the morbidity and mortality associated with these diseases
Objectives:
-To estimate the acute graft-versus-host disease (aGVHD)-free, graft failure-free survival at day +180 after allo BMT, analyzed separately by conditioning arm/cohort
Eligibility:
* Patients age \>= 4 through 75 years
* PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below:
* PID as defined by identified genetic defect or, in the absence of a mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible
* Clinical history of at least two of the following:
* Life-threatening, organ-threatening, or severely disfiguring infection
* Protracted or recurrent infections
* Infection with an opportunistic organism
* Chronic elevation in the blood of a latent virus
* Evidence of immune dysregulation
* Hypogammaglobulinemia/dysglobulinemia
* Hematologic malignancy or lymphoproliferative disorder
* Virus-associated solid tumor malignancy or pre-cancerous lesion
* At least one 7-8/8 (9-10/10) HLA-matched related or unrelated donor, or an HLA-haploidentical related donor
* Adequate end-organ function
* Consensus opinion by the investigative team that the patient has the potential to benefit from transplant despite existing, non-hematopoietic organ dysfunction
* Not pregnant or breastfeeding
* HIV negative
* Disease status: patients with malignancy should be referred in remission for evaluation, except in the case of virus-associated malignancy who may be referred at any time
Design:
* The study will have two arms that vary in mycophenolate mofetil (MMF) duration.
* RIC and RIC-MMF arms: pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* RIC-SHORT arm: pentostatin 4 mg/m2/day IV on days -9 and -5, low-dose cyclophosphamide orally daily on days -9 through -2; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* Bone marrow is the preferred graft source. Peripheral blood stem cells are permitted on RIC-MMF arm but not on RIC-SHORT arm.
* GVHD prophylaxis:
* High-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +35 for all arms except the RIC-MMF and RIC-SHORT arm. The RICMMF arm will receive MMF of varying durations based on a duration de-escalation schema.
* RIC-SHORT: Reduced-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +18 for all arms.
* Primary immunodeficiency diseases (PIDs) are conditions associated with major quantitative or qualitative immunologic abnormalities that are, in most cases, due to defects in cells of hematopoietic origin
* Participants with PID can have life-threatening complications including malignancy, recurrent infection, and autoimmunity/immune dysregulation
* Allogeneic blood or marrow transplantation (allo BMT) has the potential to cure the immune defect in PID and thereby reduce the morbidity and mortality associated with these diseases
Objectives:
-To estimate the acute graft-versus-host disease (aGVHD)-free, graft failure-free survival at day +180 after allo BMT, analyzed separately by conditioning arm/cohort
Eligibility:
* Patients age \>= 4 through 75 years
* PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below:
* PID as defined by identified genetic defect or, in the absence of a mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible
* Clinical history of at least two of the following:
* Life-threatening, organ-threatening, or severely disfiguring infection
* Protracted or recurrent infections
* Infection with an opportunistic organism
* Chronic elevation in the blood of a latent virus
* Evidence of immune dysregulation
* Hypogammaglobulinemia/dysglobulinemia
* Hematologic malignancy or lymphoproliferative disorder
* Virus-associated solid tumor malignancy or pre-cancerous lesion
* At least one 7-8/8 (9-10/10) HLA-matched related or unrelated donor, or an HLA-haploidentical related donor
* Adequate end-organ function
* Consensus opinion by the investigative team that the patient has the potential to benefit from transplant despite existing, non-hematopoietic organ dysfunction
* Not pregnant or breastfeeding
* HIV negative
* Disease status: patients with malignancy should be referred in remission for evaluation, except in the case of virus-associated malignancy who may be referred at any time
Design:
* The study will have two arms that vary in mycophenolate mofetil (MMF) duration.
* RIC and RIC-MMF arms: pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* RIC-SHORT arm: pentostatin 4 mg/m2/day IV on days -9 and -5, low-dose cyclophosphamide orally daily on days -9 through -2; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* Bone marrow is the preferred graft source. Peripheral blood stem cells are permitted on RIC-MMF arm but not on RIC-SHORT arm.
* GVHD prophylaxis:
* High-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +35 for all arms except the RIC-MMF and RIC-SHORT arm. The RICMMF arm will receive MMF of varying durations based on a duration de-escalation schema.
* RIC-SHORT: Reduced-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +18 for all arms.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 16-C-0003 | None | None | View |