Ignite Creation Date:
2024-05-06 @ 8:28 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06398457
Status:
RECRUITING
Last Update Posted:
2024-07-11
First Post:
2024-05-01
Brief Title:
Darzalex Faspro Daratumumab and Hyaluronidase-fihj Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
A Pilot Study of Darzalex Faspro Daratumumab and Hyaluronidase-fihj Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies
Status:
RECRUITING
Status Verified Date:
2024-09
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:
This research is being done to investigate the safety and effectiveness of Darzalex Faspro daratumumab and hyaluronidase-fihj a monoclonal antibody that targets plasma cells that make antibodies and whether it can lower donor specific antibodies DSA levels to low enough levels to permit patients to proceed with allogeneic peripheral blood transplant alloBMT Those being asked to participate have high DSA levels that puts those being asked to participate at high risk of rejecting the available donors blood stem cells and making those being asked to participate ineligible to receive a stem cell transplant
Detailed Description:
Allogeneic blood or bone marrow transplant alloBMT remains the definitive curative treatment for many with relapsed or refractory hematologic malignancies In recent years increased use of alternative non-fully human leukocyte antigen HLA-matched donors has led to increased rates of donor specific antibodies DSA DSA are pre-formed HLA-antibodies in the recipient directed against the donors class I andor class II HLA antigens DSA can be formed by exposure to foreign HLA antigens most commonly by pregnancy blood transfusions and previous organ or blood transplantation
High levels of circulating anti-HLA antibodies directed towards mismatched donor HLA antigens at the time of alloBMT can dramatically increase the risk of primary graft failure PGF The strength of these donor specific antibodies DSA can be assessed with several methodologies including cross-matched cellular based assays cytotoxic or flow cytometric assessment or the more sensitive solid phase immunoassay SPI that estimates antibody level Methods to desensitize patients with elevated DSAs using therapeutic plasma exchange TPE intravenous immunoglobulin IVIG and immunosuppression ie mycophenolate mofetil and tacrolimus are successful in patients with moderate levels of DSAs However in many patients the DSA levels are considered too high for desensitization or desensitization has failed to lower levels of the DSA and suitable alternative donors cannot be readily identified
In this single-institution study at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center SKCCC we will identify patients in whom alloBMT is indicated but where DSA levels are above a pre-defined threshold using a proprietary algorithm that combines information from flow cytometric crossmatch FCXM and SPI the Johns Hopkins JH-DSA Semi-Quant Screen Score Patients who meet eligibility criteria will undergo 4 weekly doses of treatment with Darzalex Faspro an anti- 38 cluster of differentiation 38 antibody that kills plasma cells and lowers immunoglobulin levels followed by standard desensitization with TPE IVIG and immunosuppression Eight subjects will be treated in this pilot study The primary endpoint will be based on safety of Darzalex Faspro and the number of patients who have DSA levels lowered enough to proceed to conditioning based on a pre-defined algorithm called JH-DSA Semi-Quant Response Score
High levels of circulating anti-HLA antibodies directed towards mismatched donor HLA antigens at the time of alloBMT can dramatically increase the risk of primary graft failure PGF The strength of these donor specific antibodies DSA can be assessed with several methodologies including cross-matched cellular based assays cytotoxic or flow cytometric assessment or the more sensitive solid phase immunoassay SPI that estimates antibody level Methods to desensitize patients with elevated DSAs using therapeutic plasma exchange TPE intravenous immunoglobulin IVIG and immunosuppression ie mycophenolate mofetil and tacrolimus are successful in patients with moderate levels of DSAs However in many patients the DSA levels are considered too high for desensitization or desensitization has failed to lower levels of the DSA and suitable alternative donors cannot be readily identified
In this single-institution study at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center SKCCC we will identify patients in whom alloBMT is indicated but where DSA levels are above a pre-defined threshold using a proprietary algorithm that combines information from flow cytometric crossmatch FCXM and SPI the Johns Hopkins JH-DSA Semi-Quant Screen Score Patients who meet eligibility criteria will undergo 4 weekly doses of treatment with Darzalex Faspro an anti- 38 cluster of differentiation 38 antibody that kills plasma cells and lowers immunoglobulin levels followed by standard desensitization with TPE IVIG and immunosuppression Eight subjects will be treated in this pilot study The primary endpoint will be based on safety of Darzalex Faspro and the number of patients who have DSA levels lowered enough to proceed to conditioning based on a pre-defined algorithm called JH-DSA Semi-Quant Response Score
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
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 |
|---|---|---|---|
| IRB00440881 | OTHER | JHM IRB | None |