Ignite Creation Date:
2024-05-06 @ 8:10 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06287944
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-01
First Post:
2024-02-16
Brief Title:
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Sponsor:
City of Hope Medical Center
Organization:
City of Hope Medical Center
Study Overview
Official Title:
Phase I Study of Escalating Doses of 225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody Added to the Conditioning Regimen of Fludarabine Melphalan and Organ Sparing Total Marrow and Lymphoid Irradiation TMLI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects best dose and effectiveness of 225Ac-DOTA-Anti-CD38 daratumumab monoclonal antibody in combination with fludarabine melphalan and total marrow and lymphoid irradiation TMLI as conditioning treatment for donor stem cell transplant in patients with high-risk acute myeloid leukemia AML acute lymphoblastic leukemia ALL and myelodysplastic syndrome MDS Daratumumab is in a class of medications called monoclonal antibodies It binds to a protein called CD38 which is found on some types of immune cells and cancer cells Daratumumab may block CD38 and help the immune system kill cancer cells Radioimmunotherapy is treatment with a radioactive substance that is linked to a monoclonal antibody such as daratumumab that will find and attach to cancer cells Radiation given off by the radioisotope my help kill the cancer cells Chemotherapy drugs such as fludarabine and melphalan work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Radiation therapy uses high energy x-rays particles or radioactive seeds to kill cancer cells and shrink tumors TMLI is a targeted form of body radiation that targets marrow lymph node chains and the spleen It is designed to reduce radiation-associated side effects and maximize therapy effect Actinium Ac 225-DOTA-daratumumab combined with fludarabine melphalan and TMLI may be safe tolerable andor effective as conditioning treatment for donor stem cell transplant in patients with high-risk AML ALL and MDS
Detailed Description:
PRIMARY OBJECTIVES
I Describe toxicities attributable to actinium Ac 225-DOTA-daratumumab 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy by dose level in patients treated under this regimen
II Determine the maximum tolerated doserecommended phase II dose MTDRP2D of 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy with fixed doses of organ sparing TMLI 12 Gy fludarabine and melphalan FM100 as conditioning regimen for allogeneic hematopoietic cell transplantation HCT for treatment of high-risk acute myeloid leukemias acute lymphoblastic leukemia or myelodysplastic syndrome MDS in patients who are not eligible for standard myeloablative regimens
SECONDARY OBJECTIVES
I Evaluate the safety of the regimen at each dose level by assessing the following
Ia Type frequency severity attribution time course and duration of adverse events including acutechronic graft-versus-host disease GVHD infection and delayed engraftment
II Estimate overall survival OS event-free survival EFS GVHD relapse free survival GRFS cumulative incidence CI of relapseprogression and non-relapse mortality NRM at 100 days 1 year and 2 years
III Describe biodistribution pharmacokinetics and organ dosimetry of 225Ac-DOTA-daratumumab
OUTLINE This is a dose escalation of actinium Ac 225-DOTA-Daratumumab in combination with fludarabine melphalan and TMLI
Patients receive daratumumab intravenously IV over 45 minutes followed by indium In 111-DOTA-daratumumab IV over 15 minutes and actinium Ac 225-DOTA-daratumumab IV over 20-40 minutes on day -15 Patients receive TMLI twice daily BID on days -8 to -5 fludarabine IV on days -4 to -2 and melphalan IV on day -2 followed by HCT on day 0 Patients receive GVHD prophylaxis with sirolimus and tacrolimus starting on day -1 Patients also undergo computed tomography CT during screening nuclear scan and single photon emission computed tomography SPECT scans on study bone marrow biopsy and aspiration echocardiography or multigated acquisition scan MUGA and blood sample collection during screening and throughout study
After completion of study treatment patients are followed up twice weekly for the first 100 days post-transplant then twice monthly up to 6 months post-transplant followed by monthly until discontinuation of immunosuppressive therapy without evidence of GVHD with at least yearly follow-up for 2 years
I Describe toxicities attributable to actinium Ac 225-DOTA-daratumumab 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy by dose level in patients treated under this regimen
II Determine the maximum tolerated doserecommended phase II dose MTDRP2D of 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy with fixed doses of organ sparing TMLI 12 Gy fludarabine and melphalan FM100 as conditioning regimen for allogeneic hematopoietic cell transplantation HCT for treatment of high-risk acute myeloid leukemias acute lymphoblastic leukemia or myelodysplastic syndrome MDS in patients who are not eligible for standard myeloablative regimens
SECONDARY OBJECTIVES
I Evaluate the safety of the regimen at each dose level by assessing the following
Ia Type frequency severity attribution time course and duration of adverse events including acutechronic graft-versus-host disease GVHD infection and delayed engraftment
II Estimate overall survival OS event-free survival EFS GVHD relapse free survival GRFS cumulative incidence CI of relapseprogression and non-relapse mortality NRM at 100 days 1 year and 2 years
III Describe biodistribution pharmacokinetics and organ dosimetry of 225Ac-DOTA-daratumumab
OUTLINE This is a dose escalation of actinium Ac 225-DOTA-Daratumumab in combination with fludarabine melphalan and TMLI
Patients receive daratumumab intravenously IV over 45 minutes followed by indium In 111-DOTA-daratumumab IV over 15 minutes and actinium Ac 225-DOTA-daratumumab IV over 20-40 minutes on day -15 Patients receive TMLI twice daily BID on days -8 to -5 fludarabine IV on days -4 to -2 and melphalan IV on day -2 followed by HCT on day 0 Patients receive GVHD prophylaxis with sirolimus and tacrolimus starting on day -1 Patients also undergo computed tomography CT during screening nuclear scan and single photon emission computed tomography SPECT scans on study bone marrow biopsy and aspiration echocardiography or multigated acquisition scan MUGA and blood sample collection during screening and throughout study
After completion of study treatment patients are followed up twice weekly for the first 100 days post-transplant then twice monthly up to 6 months post-transplant followed by monthly until discontinuation of immunosuppressive therapy without evidence of GVHD with at least yearly follow-up for 2 years
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 |
|---|---|---|---|
| P30CA033572 | NIH | City of Hope Medical Center | httpsreporternihgovquickSearchP30CA033572 |
| NCI-2024-01131 | REGISTRY | None | None |
| 23694 | OTHER | None | None |