search
Back to results

Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

Primary Purpose

Primary T-cell Immunodeficiency Disorders, Common Variable Immunodeficiency, Immune System Diseases

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Immunosuppression Only Conditioning -Closed with amendment L
Reduced Intensity Conditioning
Myeloablative Conditioning-Closed with amendment L
GVHD Prophylaxis
Allo BMT
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary T-cell Immunodeficiency Disorders focused on measuring Haploidentical, Autoimmunity, Immune Dysregulation, Congenital, Opportunistic Infection

Eligibility Criteria

4 Years - 75 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers
  • INCLUSION CRITERIA - RECIPIENT:
  • Patients age greater than or equal to 4 through 75 years
  • PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below:

    1. PID as defined by identified genetic defect or, in the absence of a PID-associated genetic mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible upon discussion with the PI

      • Mutations should be confirmed in a CLIA-certified laboratory, if such testing is available.
      • Patients without a mutation must be deemed eligible and appropriate for allo BMT by the PI. Some patients may meet the clinical history criteria listed below, but will not be eligible if it is thought that their clinical history is due to a condition apart from an immune defect. In addition, patients with a PID of mild severity, such as those with selective IgA deficiency, may meet at least two of the clinical history criteria, but may be deemed inappropriate for allo BMT by the PI if it is felt that the risks of the procedure outweigh the severity of the disease.
    2. Clinical history of at least two of the following:

      • Life-threatening, organ-threatening, or severely disfiguring infection
      • Protracted or recurrent infections requiring unusually long or repeated courses of antibiotics
      • Infection with an opportunistic organism
      • Chronic elevation in the blood (greater than or equal to 2 documented elevations over a period of 6 months or longer) of a latent virus (EBV, CMV, HHV6, HHV8, etc.)
      • Evidence of immune dysregulation, as manifested by autoimmune disease, atopy, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, granulomas, splenomegaly, or lymphadenopathy
      • Patients with hemophagocytic lymphohistiocytosis or macrophage activation syndrome related to an underlying lymphoma with no other clinical history suggestive of a primary immunodeficiency will not be eligible
      • Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination
      • Hematologic malignancy or lymphoproliferative disorder
      • Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available
      • Virus-associated solid tumor malignancy or pre-cancerous lesion
      • Tissue diagnosis should be confirmed by NCI Departmentof Pathology, if prior biopsies are available
  • Availability of at least one 7-8/8 (9-10/10) HLA-matched related (excluding an identical twin) or unrelated donor, or an HLA-haploidentical related donor
  • Consensus among the PI, key AIs, and consultants (as necessary) that correction of the patient s immune system through BMT has the potential to improve the patient s health, quality of life, and/or life expectancy, after taking into consideration the patient s existing non-hematopoietic, potentially irreversible organ dysfunction
  • Adequate end-organ function, as measured by:

    • Left ventricular ejection fraction (LVEF) greater than or equal to 40% by 2D echocardiogram (ECHO) or MUGA, or left ventricular shortening fraction greater than or equal to 20% by ECHO for patients receiving RIC or RIC-MMF, or LVEF greater than or equal to 30% if the patient has radiologic evidence of aortic, renal, or coronary artery vasculitis.
    • Pulmonary function tests: DL(co) (corrected for hemoglobin) and FEV(1) greater than or equal to 40% of predicted for the RIC and RIC-MMF arms; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation >92% on room air. Calculations will be based on the values reported in CRIS.
    • Bilirubin less than or equal to 3.0 mg/dL (unless due to Gilbert s syndrome or hemolysis) for patients receiving RIC or RIC-MMF; ALT and AST less than or equal to 10 times ULN for patients receiving RIC or RIC-MMF. Patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC or RIC-MMF arms if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with bone marrow transplant.
    • Estimated creatinine clearance of greater than or equal to 40 mL/min/1.73 m(2), calculated using the Cockcroft-Gault equation for adults and Schwartz formula for pediatric patients, for patients with creatinine levels above the institutional upper limit of normal
  • Karnofsky or Lansky performance status of greater than or equal to 60% or ECOG performance status of 2 or less
  • Ability of subject to understand and the willingness to sign a written informed consent document
  • Not pregnant or breastfeeding. As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo BMT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.
  • Disease status: Patients with malignancy are to be referred in remission for evaluation, except in cases of virus-associated malignancy who may be referred at any time. Should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to his/her primary hematologist-oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study, although this should only occur as a bridge to transplant. If under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off the study. Patients receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.

EXCLUSION CRITERIA - RECIPIENT:

  • Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo BMT.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, G-CSF) used in the study
  • Active psychiatric disorder which may compromise compliance with the transplant protocol, or which does not allow for appropriate informed consent
  • Active central nervous system (CNS) involvement by malignancy, except in cases of virus-associated malignancies with CNS involvement in which case the patient may benefit from the transplant to control the malignancy.
  • MAGT1 mutation and active need to take anti-platelet agents and/or therapeutic anti-coagulation that cannot be interrupted during aplasia.
  • HIV positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of PID severity and/or the attribution of clinical manifestations of immunodeficiency to a PID.
  • Lack of adequate central venous access potential

Inclusion Criteria (Related Donor):

  • Ages greater than equal to 4
  • Related donor deemed suitable and eligible and willing to donate per clinical evalations who are additionally willing to donate blood, urine, and marrow specimens for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors but is not required for clinical donation, so it is possible that not all related donors will enroll on this study.

Exclusion Criteria (Related Donor):

None

INCLUSION CRITERIA - UNRELATED DONOR:

  • Ages greater than equal to 18
  • Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/, except for the additional requirement of EBV serostatus testing. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study.

EXCLUSION CRITERIA - UNRELATED DONOR:

-Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting
  • National Marrow Donor ProgramRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

No Intervention

Arm Label

1/ IOC Arm-Closed with amendment L (07/05/2019)

2/ RIC Arm - Closed with Amendment L (07/05/2019)

3/ MAC Arm-Closed with amendment L (07/05/2019)

4/ RIC-MMF Arm

5/ Donor Arm

Arm Description

Immunosuppression Only Conditioning Arm

Reduced Intensity Conditioning Arm

Myeloablative Conditioning Arm

Reduced Intensity Conditioning with MMF duration de-escalation design

Donor

Outcomes

Primary Outcome Measures

For the RIC-MMF arm: To determine the shortest duration of MMF that can be safely administered without excessive rates of graft failure or acute grade 3-4 GVHD
Shortest duration of MMF
For the RIC : To estimate the aGVHD-free, graft failure-free survival
Proportion of participants without GVHD

Secondary Outcome Measures

Transplant-related mortality
Cumulative incidence of transplant-related mortality at 180 days and 1 year post transplant.
Secondary graft failure
Cumulative incidence of secondary graft failure at 1 year post transplant.
Overall survival
Time from transplant to death of any cause.
Kinetics and durability of lineage-specific donor chimerism
Median amount of patient who has early chimerism
Kinetics and durability of engraftment
The percentage of donor T-, B-, NK-, and myeloid cell populations at days +28, +42, +60, +100, +180, and 1 year post transplant.
Incidence of Chronic Graft-versus-host disease
Cumulative incidence of chronic graft versus host disease at 1 and 2 years post transplant.
Incidence of Acute Graft-versus-host disease
Cumulative incidence of acute graft versus host disease at 1 year post transplant
Event-free survival
Time from transplant to death of any cause or other event, including disease relapse, graft failure, grade 3-4 acute GVHD, chronic GVHD requiring systemic therapy, or receipt of post-transplant donor cell infusion.
Disease free survival
Time from transplant to death of any cause or disease relapse.

Full Information

First Posted
October 16, 2015
Last Updated
October 13, 2023
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02579967
Brief Title
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Official Title
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Study Type
Interventional

2. Study Status

Record Verification Date
September 21, 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2015 (Actual)
Primary Completion Date
December 21, 2027 (Anticipated)
Study Completion Date
December 21, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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 greater than or equal to 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. Bone marrow is the preferred graft source. Peripheral blood stem cells are permitted 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 arm. The RIC-MMF arm will receive MMF of varying durations based on a duration de-escalation schema. Participants with DNA repair/telomere defects/familial cancer syndromes may receive a reduced dose (25 mg/kg/day) PTCy on days +3 and +4, in addition to sirolimus and MMF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary T-cell Immunodeficiency Disorders, Common Variable Immunodeficiency, Immune System Diseases, Autoimmune Lymphoproliferative, Lymphoproliferative Disorders
Keywords
Haploidentical, Autoimmunity, Immune Dysregulation, Congenital, Opportunistic Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
224 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1/ IOC Arm-Closed with amendment L (07/05/2019)
Arm Type
Experimental
Arm Description
Immunosuppression Only Conditioning Arm
Arm Title
2/ RIC Arm - Closed with Amendment L (07/05/2019)
Arm Type
Experimental
Arm Description
Reduced Intensity Conditioning Arm
Arm Title
3/ MAC Arm-Closed with amendment L (07/05/2019)
Arm Type
Experimental
Arm Description
Myeloablative Conditioning Arm
Arm Title
4/ RIC-MMF Arm
Arm Type
Experimental
Arm Description
Reduced Intensity Conditioning with MMF duration de-escalation design
Arm Title
5/ Donor Arm
Arm Type
No Intervention
Arm Description
Donor
Intervention Type
Drug
Intervention Name(s)
Immunosuppression Only Conditioning -Closed with amendment L
Intervention Description
Pentostatin 4 mg/m2/day IV on days -9 and -5, cyclophosphamide 5 mg/kg orally daily on days -9 through -2 (Closed with amendment L)
Intervention Type
Drug
Intervention Name(s)
Reduced Intensity Conditioning
Intervention Description
pentostatin 4 mg/m2/day IV on days -11 and -7, cyclophosphamide 3 mg/kg orally daily on days -11 through -4; busulfan IV, pharmokinetically dosed, on days -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Myeloablative Conditioning-Closed with amendment L
Intervention Description
Pentostatin 4 mg/m2/day IV on days -13 and -9, low-dose cyclophosphamide orally daily on days -13 through -6; busulfan IV, pharmokinetically dosed, on days -5, -4, -3, and -2. (Closed with amendment L)
Intervention Type
Drug
Intervention Name(s)
GVHD Prophylaxis
Intervention Description
High-dose, post-transplantation cyclophosphamide (PTCy) 25-50 mg/kg on days +3 and +4, sirolimus 6 mg on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through 0, +18, +25, or +35 depending on treatment arm and cohort.
Intervention Type
Procedure
Intervention Name(s)
Allo BMT
Intervention Description
Allogeneic blood or marrow transplantation
Primary Outcome Measure Information:
Title
For the RIC-MMF arm: To determine the shortest duration of MMF that can be safely administered without excessive rates of graft failure or acute grade 3-4 GVHD
Description
Shortest duration of MMF
Time Frame
Duration de-escalation design
Title
For the RIC : To estimate the aGVHD-free, graft failure-free survival
Description
Proportion of participants without GVHD
Time Frame
+180 after allo BMT
Secondary Outcome Measure Information:
Title
Transplant-related mortality
Description
Cumulative incidence of transplant-related mortality at 180 days and 1 year post transplant.
Time Frame
+180 and 1 year post transplant
Title
Secondary graft failure
Description
Cumulative incidence of secondary graft failure at 1 year post transplant.
Time Frame
1 year post transplant
Title
Overall survival
Description
Time from transplant to death of any cause.
Time Frame
1 year post transplant
Title
Kinetics and durability of lineage-specific donor chimerism
Description
Median amount of patient who has early chimerism
Time Frame
days +28 and +42
Title
Kinetics and durability of engraftment
Description
The percentage of donor T-, B-, NK-, and myeloid cell populations at days +28, +42, +60, +100, +180, and 1 year post transplant.
Time Frame
days +28, +42, +60, +100, +180, and 1 year after allo BMT
Title
Incidence of Chronic Graft-versus-host disease
Description
Cumulative incidence of chronic graft versus host disease at 1 and 2 years post transplant.
Time Frame
1 and 2 years post transplant
Title
Incidence of Acute Graft-versus-host disease
Description
Cumulative incidence of acute graft versus host disease at 1 year post transplant
Time Frame
1 year post transplant
Title
Event-free survival
Description
Time from transplant to death of any cause or other event, including disease relapse, graft failure, grade 3-4 acute GVHD, chronic GVHD requiring systemic therapy, or receipt of post-transplant donor cell infusion.
Time Frame
1 year post transplant
Title
Disease free survival
Description
Time from transplant to death of any cause or disease relapse.
Time Frame
1 year post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA - RECIPIENT: Patients age greater than or equal to 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 PID-associated genetic mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible upon discussion with the PI Mutations should be confirmed in a CLIA-certified laboratory, if such testing is available. Patients without a mutation must be deemed eligible and appropriate for allo BMT by the PI. Some patients may meet the clinical history criteria listed below, but will not be eligible if it is thought that their clinical history is due to a condition apart from an immune defect. In addition, patients with a PID of mild severity, such as those with selective IgA deficiency, may meet at least two of the clinical history criteria, but may be deemed inappropriate for allo BMT by the PI if it is felt that the risks of the procedure outweigh the severity of the disease. Clinical history of at least two of the following: Life-threatening, organ-threatening, or severely disfiguring infection Protracted or recurrent infections requiring unusually long or repeated courses of antibiotics Infection with an opportunistic organism Chronic elevation in the blood (greater than or equal to 2 documented elevations over a period of 6 months or longer) of a latent virus (EBV, CMV, HHV6, HHV8, etc.) Evidence of immune dysregulation, as manifested by autoimmune disease, atopy, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, granulomas, splenomegaly, or lymphadenopathy Patients with hemophagocytic lymphohistiocytosis or macrophage activation syndrome related to an underlying lymphoma with no other clinical history suggestive of a primary immunodeficiency will not be eligible Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination Hematologic malignancy or lymphoproliferative disorder Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available Virus-associated solid tumor malignancy or pre-cancerous lesion Tissue diagnosis should be confirmed by NCI Departmentof Pathology, if prior biopsies are available Availability of at least one 7-8/8 (9-10/10) HLA-matched related (excluding an identical twin) or unrelated donor, or an HLA-haploidentical related donor Consensus among the PI, key AIs, and consultants (as necessary) that correction of the patient s immune system through BMT has the potential to improve the patient s health, quality of life, and/or life expectancy, after taking into consideration the patient s existing non-hematopoietic, potentially irreversible organ dysfunction Adequate end-organ function, as measured by: Left ventricular ejection fraction (LVEF) greater than or equal to 40% by 2D echocardiogram (ECHO) or MUGA, or left ventricular shortening fraction greater than or equal to 20% by ECHO for patients receiving RIC or RIC-MMF, or LVEF greater than or equal to 30% if the patient has radiologic evidence of aortic, renal, or coronary artery vasculitis. Pulmonary function tests: DL(co) (corrected for hemoglobin) and FEV(1) greater than or equal to 40% of predicted for the RIC and RIC-MMF arms; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation >92% on room air. Calculations will be based on the values reported in CRIS. Bilirubin less than or equal to 3.0 mg/dL (unless due to Gilbert s syndrome or hemolysis) for patients receiving RIC or RIC-MMF; ALT and AST less than or equal to 10 times ULN for patients receiving RIC or RIC-MMF. Patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC or RIC-MMF arms if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with bone marrow transplant. Estimated creatinine clearance of greater than or equal to 40 mL/min/1.73 m(2), calculated using the Cockcroft-Gault equation for adults and Schwartz formula for pediatric patients, for patients with creatinine levels above the institutional upper limit of normal Karnofsky or Lansky performance status of greater than or equal to 60% or ECOG performance status of 2 or less Ability of subject to understand and the willingness to sign a written informed consent document Not pregnant or breastfeeding. As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo BMT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately. Disease status: Patients with malignancy are to be referred in remission for evaluation, except in cases of virus-associated malignancy who may be referred at any time. Should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to his/her primary hematologist-oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study, although this should only occur as a bridge to transplant. If under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off the study. Patients receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol. EXCLUSION CRITERIA - RECIPIENT: Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo BMT. History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, G-CSF) used in the study Active psychiatric disorder which may compromise compliance with the transplant protocol, or which does not allow for appropriate informed consent Active central nervous system (CNS) involvement by malignancy, except in cases of virus-associated malignancies with CNS involvement in which case the patient may benefit from the transplant to control the malignancy. MAGT1 mutation and active need to take anti-platelet agents and/or therapeutic anti-coagulation that cannot be interrupted during aplasia. HIV positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of PID severity and/or the attribution of clinical manifestations of immunodeficiency to a PID. Lack of adequate central venous access potential Inclusion Criteria (Related Donor): Ages greater than equal to 4 Related donor deemed suitable and eligible and willing to donate per clinical evalations who are additionally willing to donate blood, urine, and marrow specimens for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors but is not required for clinical donation, so it is possible that not all related donors will enroll on this study. Exclusion Criteria (Related Donor): None INCLUSION CRITERIA - UNRELATED DONOR: Ages greater than equal to 18 Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/, except for the additional requirement of EBV serostatus testing. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study. EXCLUSION CRITERIA - UNRELATED DONOR: -Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dimana Dimitrova, M.D.
Phone
(240) 858-3647
Email
dimana.dimitrova@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dimana Dimitrova, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone
888-624-1937
Facility Name
National Marrow Donor Program
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55413-1753
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Miller, M.D.
Phone
763-406-8566
Email
jmiller@nmdp.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGAP
IPD Sharing Time Frame
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active.
IPD Sharing Access Criteria
Clinical data will be made available and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians
Citations:
PubMed Identifier
23423745
Citation
Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013 Apr 1;31(10):1310-6. doi: 10.1200/JCO.2012.44.3523. Epub 2013 Feb 19.
Results Reference
background
PubMed Identifier
21130889
Citation
Mariotti J, Taylor J, Massey PR, Ryan K, Foley J, Buxhoeveden N, Felizardo TC, Amarnath S, Mossoba ME, Fowler DH. The pentostatin plus cyclophosphamide nonmyeloablative regimen induces durable host T cell functional deficits and prevents murine marrow allograft rejection. Biol Blood Marrow Transplant. 2011 May;17(5):620-31. doi: 10.1016/j.bbmt.2010.11.029. Epub 2010 Dec 3.
Results Reference
background
PubMed Identifier
25459185
Citation
Kang E, Gennery A. Hematopoietic stem cell transplantation for primary immunodeficiencies. Hematol Oncol Clin North Am. 2014 Dec;28(6):1157-70. doi: 10.1016/j.hoc.2014.08.006. Epub 2014 Sep 16.
Results Reference
background
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2016-C-0003.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

We'll reach out to this number within 24 hrs