Ignite Creation Date:
2024-05-06 @ 7:08 PM
Last Modification Date:
2024-10-26 @ 3:01 PM
Study NCT ID:
NCT05907746
Status:
RECRUITING
Last Update Posted:
2024-07-05
First Post:
2023-06-15
Brief Title:
Allogeneic Hematopoietic Stem Cell Transplantation With JSP191-Based Conditioning in Participants With GATA2 Deficiency
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With JSP191-Based Conditioning in Participants With GATA2 Deficiency
Status:
RECRUITING
Status Verified Date:
2024-10-18
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
People with GATA2 deficiency have a mutation on the GATA2 gene This gene affects immune function People with this disease are prone to serious infections in time they may develop blood cancers A hematopoietic stem cell HSC transplant can cure GATA2 deficiency but using stem cells donated by other people can cause serious side effects
Objective
To test a new drug JSP191 to see if it can make HSC transplants safer
Eligibility
People aged 6 to 70 years who have GATA2 deficiency
Design
Participants will be screened They will have a physical exam with blood and urine tests They will have tests of their heart and lung function They may have a bone marrow biopsy Their hip will be numbed a large needle will be inserted to draw out tissue from inside the pelvis
Participants will have a central venous catheter placed in a vein of the neck or chest This will be used to draw blood and administer drugs
JSP191 will be given through the catheter about 11 days before the transplant This is part of conditioning preparing the body to receive the new stem cells Conditioning also includes other medications and total body irradiation
Donor stem cells will be administered through the catheter Participants will receive other approved drugs to help prevent side effects
Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant They will remain in the local area for 100 days after discharge they will come to the clinic at least once a week during this time Follow-up visits will continue for 3 years
People with GATA2 deficiency have a mutation on the GATA2 gene This gene affects immune function People with this disease are prone to serious infections in time they may develop blood cancers A hematopoietic stem cell HSC transplant can cure GATA2 deficiency but using stem cells donated by other people can cause serious side effects
Objective
To test a new drug JSP191 to see if it can make HSC transplants safer
Eligibility
People aged 6 to 70 years who have GATA2 deficiency
Design
Participants will be screened They will have a physical exam with blood and urine tests They will have tests of their heart and lung function They may have a bone marrow biopsy Their hip will be numbed a large needle will be inserted to draw out tissue from inside the pelvis
Participants will have a central venous catheter placed in a vein of the neck or chest This will be used to draw blood and administer drugs
JSP191 will be given through the catheter about 11 days before the transplant This is part of conditioning preparing the body to receive the new stem cells Conditioning also includes other medications and total body irradiation
Donor stem cells will be administered through the catheter Participants will receive other approved drugs to help prevent side effects
Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant They will remain in the local area for 100 days after discharge they will come to the clinic at least once a week during this time Follow-up visits will continue for 3 years
Detailed Description:
Background
GATA2 deficiency an immunodeficiency and bone marrow failure disorder due to inherited or sporadic mutations in or loss of one allele of the GATA2 gene is characterized by 1 nontuberculous mycobacteria NTM and other opportunistic infections 2 deficiency of monocytes B lymphocytes and Natural Killer NK cells in the peripheral blood and 3 progression to myelodysplastic syndrome MDS chronic myelomonocytic leukemia CMML and acute myelogenous leukemia AML
Allogeneic hematopoietic cell transplantation HCT appears to be curative and interim results from protocol 13-C-0132 NCT01861106 demonstrated a 2-year event-free survival rate of 83 for 59 participants with GATA2 deficiency who underwent HCT with a busulfan-based conditioning regimen
However traditional HCT approaches using alkylating agents such as busulfan continue to place recipients at risk for potentially life-threatening transplant-related toxicities as well as late effects such as infertility and secondary malignancy
JSP191 is a humanized glycosylated IgG1 monoclonal antibody that targets CD117 human c-Kit present on endogenous hematopoietic stem cells HSC JSP191 has been shown in pre-clinical and early clinical studies to safely deplete human and non-human primate HSC with minimal toxicity
Primary Objective
-To determine whether allogeneic hematopoietic cell transplantation with JSP191-based conditioning results in sustained donor engraftment by 100 days post-transplant in participants with GATA2 deficiency
Eligibility
Recipients aged 6-70 years old with pathogenic germline mutations in GATA2 and clinical manifestations consistent with a diagnosis of GATA2 deficiency
Have an 88 Human leukocyte antigen HLA-matched related or unrelated donor or a 78 HLA-matched unrelated donor or haploidentical related donor
Have early stage GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5 blasts and normal or favorable cytogenetics defined as good or very good cytogenetics risk groups plus trisomy 8
Design
All participants with GATA2 deficiency will receive a pre-transplant conditioning regimen consisting of JSP191 administered as a single intravenous IV infusion between day -13 and -8 depending on body weight day -11 range day -13 to -10 for participants 35 kg day -9 for participants 35 kg but 15 kg or day -8 for participants 15 kg followed by fludarabine or fludarabinecyclophosphamide IV infusions 3 or 5 days depending on the donor and 200 cGy total body irradiation TBI on day -1 HCT will be infused on day 0
Participants with an 88 HLA-matched related or unrelated donor assigned to Arm A will receive a fludarabine for three days on days -4 -3 and -2
Participants with a 78 HLA-matched unrelated donor or a haploidentical related donor assigned to Arm B will receive a fludarabine for five days on days -6 -5 -4 -3 and -2 cyclophosphamide for 2 days on days -6 and -5
Post-transplant immunosuppression for Graft Versus Host Disease GVHD prophylaxis for recipients of Arms A and B will consist of cyclophosphamide for 2 days on days 3 and 4 along with mycophenolate mofetil from day 5 to approximately day 35 and tacrolimus from day 5 to approximately day 180 If there is no evidence of GVHD tacrolimus will be stopped or tapered at approximately day 180
GATA2 deficiency an immunodeficiency and bone marrow failure disorder due to inherited or sporadic mutations in or loss of one allele of the GATA2 gene is characterized by 1 nontuberculous mycobacteria NTM and other opportunistic infections 2 deficiency of monocytes B lymphocytes and Natural Killer NK cells in the peripheral blood and 3 progression to myelodysplastic syndrome MDS chronic myelomonocytic leukemia CMML and acute myelogenous leukemia AML
Allogeneic hematopoietic cell transplantation HCT appears to be curative and interim results from protocol 13-C-0132 NCT01861106 demonstrated a 2-year event-free survival rate of 83 for 59 participants with GATA2 deficiency who underwent HCT with a busulfan-based conditioning regimen
However traditional HCT approaches using alkylating agents such as busulfan continue to place recipients at risk for potentially life-threatening transplant-related toxicities as well as late effects such as infertility and secondary malignancy
JSP191 is a humanized glycosylated IgG1 monoclonal antibody that targets CD117 human c-Kit present on endogenous hematopoietic stem cells HSC JSP191 has been shown in pre-clinical and early clinical studies to safely deplete human and non-human primate HSC with minimal toxicity
Primary Objective
-To determine whether allogeneic hematopoietic cell transplantation with JSP191-based conditioning results in sustained donor engraftment by 100 days post-transplant in participants with GATA2 deficiency
Eligibility
Recipients aged 6-70 years old with pathogenic germline mutations in GATA2 and clinical manifestations consistent with a diagnosis of GATA2 deficiency
Have an 88 Human leukocyte antigen HLA-matched related or unrelated donor or a 78 HLA-matched unrelated donor or haploidentical related donor
Have early stage GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5 blasts and normal or favorable cytogenetics defined as good or very good cytogenetics risk groups plus trisomy 8
Design
All participants with GATA2 deficiency will receive a pre-transplant conditioning regimen consisting of JSP191 administered as a single intravenous IV infusion between day -13 and -8 depending on body weight day -11 range day -13 to -10 for participants 35 kg day -9 for participants 35 kg but 15 kg or day -8 for participants 15 kg followed by fludarabine or fludarabinecyclophosphamide IV infusions 3 or 5 days depending on the donor and 200 cGy total body irradiation TBI on day -1 HCT will be infused on day 0
Participants with an 88 HLA-matched related or unrelated donor assigned to Arm A will receive a fludarabine for three days on days -4 -3 and -2
Participants with a 78 HLA-matched unrelated donor or a haploidentical related donor assigned to Arm B will receive a fludarabine for five days on days -6 -5 -4 -3 and -2 cyclophosphamide for 2 days on days -6 and -5
Post-transplant immunosuppression for Graft Versus Host Disease GVHD prophylaxis for recipients of Arms A and B will consist of cyclophosphamide for 2 days on days 3 and 4 along with mycophenolate mofetil from day 5 to approximately day 35 and tacrolimus from day 5 to approximately day 180 If there is no evidence of GVHD tacrolimus will be stopped or tapered at approximately day 180
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001531-C | None | None | None |