Iomab-B
[THERAPEUTIC_PROFILE]
Relapsed/Refractory AML
A small molecule protein degrader
[3D_INTERACTIVE_CONFORMATION]
[CLINICAL_TRIALS_REGISTRY]
A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 6 months from time of initial CR or CRp
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Over a 5 year period
Analysis Window: Over a 5 year period
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT
Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.
[DOSING_&_INTERVENTION_SPECIFICITIES]
No dosing specifics documented.
No dosing specifics documented.
No dosing specifics documented.
An Adaptive, Operationally Seamless Phase II / III Study of 131I-apamistamab-Led Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia With Active Disease
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 5 years post-randomization
Analysis Window: Day 28 post-HSCT
Analysis Window: Up to 6 months post-HSCT
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 5 years post-randomization
Analysis Window: 6 months post-HSCT and up to 5 years post-randomization
Analysis Window: Day 28 post-HSCT and up to 12 months
Analysis Window: Up to 5 years post-randomization
Analysis Window: Up to 5 years post-HSCT
Analysis Window: 1 year and 2 years post-HSCT
Analysis Window: Day 100 post-HSCT
Analysis Window: Up to Day 100 post-HSCT
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Participants receive standard of care conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0 GvHD prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Iodine-131 radiolabeled anti-CD45 monoclonal antibody (apamistamab). Administered IV as a dosimetric dose followed by treatment dose.
Fludarabine phosphate, 30 mg/m² IV daily on Days -6 through -2.
Cyclophosphamide
TBI, 200 cGy on Day -1 prior to HSCT.
Unmodified, G-CSF-mobilized donor stem cells infused on Day 0.
IOMAB-ACT: A Phase Ib/II Multi-institutional Study of 131 I-Apamistamab Followed by CD19-Targeted CAR-T Cell Therapy for Patients With Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Start of treatment up to 30 days post CAR T-cell infusion
Analysis Window: Screening visit to Day 100 visit
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: within 100 days of CAR T-cell infusion
Analysis Window: within 100 days of CAR T-cell infusion
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CD-19 CAR-T cell therapy
131I-Apamistamab dose will be given 5-7 days prior to a single infusion of CAR-T cell therapy
[DOSING_&_INTERVENTION_SPECIFICITIES]
single 50 mCi dose of 131I-Apamistamab given prior to CAR-T cell infusion.
CAR-T cell therapy
Hematopoietic Bone Marrow Transplantation for Patients With High-risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined With Immunosuppression Before and After Transplantation
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 30 days post-transplant
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 100 days post-transplant
Analysis Window: Up to 90 days after transplant
Analysis Window: 100 days after transplant
Analysis Window: Day 84 after transplant
Analysis Window: 2 years post-transplant
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8 via central line on day -14. NONMYELOABLATIVE CONDITIONING: Patients receive FLU IV over 30 minutes on days -6 to -2 and CY IV over 1 hour on days -6 and -5. Patients undergo TBI on day -1. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0. POST-TRANSPLATATION IMMUNOSUPPRESSION: Patients receive CY IV over 1-2 hours on day 3, MMF IV or PO TID on days 4 to 35, and tacrolimus IV over 1-2 hours or PO on days 4 to 180 with taper on day 84.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Given via central line
Given IV
Given IV
Given IV (dosimetry dose) or via central line (therapeutic dose)
Correlative studies
Given IV or PO
Given IV or PO
Undergo TBI
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 30 days after treatment
[SECONDARY_SUCCESS_ENDPOINTS]
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Participants will have relapsed or refractory B-Cell Acute Lymphoblastic Leukemia or Diffused Large B-Cell Lymphoma
[DOSING_&_INTERVENTION_SPECIFICITIES]
Patients will receive 131-I apamistamab 5-7 days prior to a single infusion of 1x10\^6 19-28z CAR T-cells/kg for those in the B-ALL cohort, or 2x10\^6 19-28z CAR T-cells/kg, for those in the DLBCL. 131-I apamistamab may be administered inpatient or outpatient at the discretion and judgment of the treating investigators.
19-28z CAR T-cells will be administered inpatient as a single infusion of 1x10\^6 19-28z CAR T-cells/kg, for those in the B-ALL cohort, or 2x10\^6 19-28z CAR T-cells/kg, for those in the DLBCL cohort. Patients will be observed inpatient for a minimum of 7 days (longer as clinically indicated and at the discretion of the treating physician).