Lintuzumab-Ac225
Actimab-A[THERAPEUTIC_PROFILE]
Relapsed/Refractory AML
A small molecule protein degrader
[3D_INTERACTIVE_CONFORMATION]
[CLINICAL_TRIALS_REGISTRY]
A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Through study completion, an average of 2.5 year
Analysis Window: Through study completion, an average of 2.5 year
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Through study completion, an average of 2.5 year
Analysis Window: Through study completion, an average of 2.5 year
Analysis Window: Through study completion, an average of 2.5 year
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Starting dose - 0.5 μCi/Kg IV infusion of Lintuzumab AC225 on Day 1 of each cycle with dose escalation 1 μCi/Kg and 1.5 μCi/Kg or de-escalation to 0.25 μCi/Kg. 1 cycle = 28 days, up to 3 to 8 cycles (depending on the cohort).
[DOSING_&_INTERVENTION_SPECIFICITIES]
Lintuzumab-Ac225 is an immunoconjugate \[antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)\] for the treatment of multiple myeloma.
A Phase I/II Study of Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Cycle 1, up to 52 days
Analysis Window: First evaluation at 42 days after treatment
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: 1 year
Analysis Window: 1 year
Analysis Window: 1 year
Analysis Window: 1 year
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Cytarabine + Lintuzumab-Ac225 Cytarabine days 1 to 10 of each cycle. Doses were divided into 2 equal fractions with the first fraction given approx. 4-7 days after 1 cycle of low dose cytarabine and the second fraction given 4-7 days after the first fraction, followed by up to 11 more cycles. Furosemide (Phase 1 only) and Spironolactone were administered after Lintuzumab-Ac225. Experimental: Phase 2 Experimental: Lintuzumab-Ac225 The Phase II dose determined during the Phase I dose escalation was 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8. Spironolactone is administered after Lintuzumab-Ac225.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Low dose cytarabine administered at 20 mg subcutaneously every 12 hours for the first 10 days (Days 1 to 10) of every cycle. Cycle 1 can last up to 52 days (depending on the schedule of study drug dosing) in order to allow for recovery from Lintuzumab-Ac225. Cycles 2-12 will last 28 days each.
In Phase 1 the starting dose level was 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4-7 days after 1 cycle of low dose cytarabine and the second fraction administered 4-7 days after the first fraction, followed by up to 11 more cycles. In Phase 2 the dose will be 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8.
40 mg by mouth daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose.
25 mg by mouth daily, administered 10 days after second dose of 225Ac-HuM195 and continued for 12 months.
A Phase I Study of Lintuzumab-Ac-225 in Combination With Venetoclax and ASTX-727 in Adults With Newly Diagnosed AML
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 28 days after the start of induction (up to 42 days for persistent neutropenia and thrombocytopenia)
Analysis Window: Up to 5 years
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to completion of dose-escalation phase (Part A)
Analysis Window: Up to 30 days after last dose of study treatment
Analysis Window: Up to 5 years
Analysis Window: Up to 5 years
Analysis Window: Up to 5 years
Analysis Window: Up to 5 years
Analysis Window: Up to 5 years
Analysis Window: Up to 5 years
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
INDUCTION: Patients receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR,PR or NR after cycle 1 receive lintuzumab-Ac225 IV over 30 minutes on day 8, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
INDUCTION: Patients receive lintuzumab-Ac225 V over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 1. RE-INDUCTION: Patients with CR, PR or NR receive lintuzumab-Ac225 IV over 30 minutes on day 1, venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of cycle 2. MAINTENANCE/CONSOLIDATION: Patients with CRi, CRh, or MLFS after cycle 1 receive venetoclax PO QD on days 1-28 and ASTX-727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Given IV
Undergo blood sample collection
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Given PO
Given PO
Lintuzumab-Ac225 Monotherapy for Patients With Hypomethylating Agent-Refractory Myelodysplastic Syndrome
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 70 days from first dose of lintuzumab-ac225
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 90 days after completion of treatment
Analysis Window: Up to 90 days after completion of treatment
Analysis Window: Up to 90 days after completion of treatment
Analysis Window: Up to 90 days after completion of treatment
Analysis Window: At baseline and after cycle 2 (cycles = 28 days)
Analysis Window: Up to 90 days after completion of treatment
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Patients receive lintuzumab-ac225 IV, over 30 minutes, on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo SPECT/CT scans and buccal swab on study, as well as bone marrow aspiration throughout the trial.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Given IV
Undergo bone marrow aspiration
Undergo buccal swab
Undergo SPECT/CT
Undergo SPECT/CT
A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Cycle 1, up to 48 days
Analysis Window: Up to 6 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 6 months
Analysis Window: End of 6 months, 12 months, 2 years
Analysis Window: End of 6 months, 12 months, 2 years
Analysis Window: Through study completion, up to 2 years
Analysis Window: Completion of Cycle 1, estimated 1 month
Analysis Window: From date of first dose until the date of first documented response, first assessment at 6 months
Analysis Window: Through study completion, up to 2 years
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Lintuzumab-Ac225 administered on Day 5 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review). Venetoclax taken on Days 1-21 of each cycle for up to 12 cycles. Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
[DOSING_&_INTERVENTION_SPECIFICITIES]
In the Phase I, patients will be enrolled into the following dose escalation cohorts: 0.50 μCi/kg, 1.0 μCi/kg, and 1.5 μCi/kg. If the 0.50 μCi/kg dose is determined to exceed the MTD, a 0.25 μCi/kg dose will be explored.
400 mg daily will be taken orally on Days 1-21 of a 28-day cycle. There will be a ramp up of venetoclax dosing in the first cycle, with 100 mg administered on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and Day 4 and later. Patients on antifungal azoles should receive one-half these doses, up to a maximum of 200 mg of venetoclax.
25 mg by mouth daily, administered on Cycle 1 Day 15 and continued for 12 months after the subject's last treatment with lintuzumab-Ac225.
A Phase I Trial of 225Ac-anti-CD33 and PD1-Inhibitor in Recurrent Glioblastoma
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Up 6 weeks after initiating treatment
Analysis Window: Up to 18 months
Analysis Window: Up to 30 days after last dose of study drug
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 2 years
Analysis Window: From randomization or initiation of treatment to the occurrence of disease progression or death, assessed up to 2 years
Analysis Window: From date of diagnosis until the patient's death from any cause, assessed up to 2 years
Analysis Window: At baseline
Analysis Window: At cycle (C) 1 day (D) 1, C1D22, C2D1, C2D22, C3D1, and C3D22 (Cycle = 42 days)
Analysis Window: At 4 hours, 24, 48, and 168 hours post-actinium Ac 225 lintuzumab (Actimab-A) during C2 (Cycle = 42 days)
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Patients receive Actimab-A IV over 30 minutes on either days 1 and 22 of cycles 1-3, days 1 and 22 of cycles 1 and 2, or days 1 and 22 of cycle 1 and day 1 of cycle 2. Patients also receive cemiplimab IV over 30 minutes on days 1 and 22 of each cycle. Cycles repeat every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and radiologic imaging throughout the study and PET/CT on study. Patients may also optionally undergo SPECT/CT on study.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Given IV
Undergo blood sample collection
Given IV
Undergo PET/CT and/or SPECT/CT
Undergo PET/CT
Undergo radiologic imaging
Undergo SPECT/CT
A Phase I/II Study of Venetoclax and Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: Cycle 1, up to 48 days
Analysis Window: Up to 6 months
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to 6 months
Analysis Window: Phase I: End of 6 months, 12 months, 24 months.
Analysis Window: Phase II: End of 6 months, 12 months, 24 months
Analysis Window: Through study completion, up to 2 years
Analysis Window: Through study completion, up to 2 years
Analysis Window: Through study completion, up to 2 years
Analysis Window: Completion of Cycle 1, estimated 1 month
Analysis Window: From date of first dose until the date of first documented response, first assessment at 6 months
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Lintuzumab-Ac225 will be administered on Day 8 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review). Venetoclax will be taken on Days 1-21 of each cycle for up to 12 cycles. Azacitidine will be administered on Days 1-7 of each cycle for up to 12 cycles. Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
[DOSING_&_INTERVENTION_SPECIFICITIES]
In the Phase I, patients will be enrolled into the following dose escalation cohorts: 0.50 μCi/kg, 1.0 μCi/kg, and 1.5 μCi/kg. If the 0.50 μCi/kg dose is determined to exceed the MTD, a 0.25 μCi/kg dose will be explored.
400 mg daily will be taken orally on Days 1-21 of a 28-day cycle. There will be a ramp up of venetoclax dosing in the first cycle, with 100 mg administered on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and Day 4 and later. Patients on antifungal azoles should receive one-half these doses, up to a maximum of 200 mg of venetoclax.
75 mg/m2 will be administered on days 1-7 of a 28-day cycle.
A Phase I Study of Lintuzumab-Ac225 in Combination with CLAG-M Chemotherapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia
[INVESTIGATORS_&_FACILITY_ROSTER]
[PRIMARY_SUCCESS_ENDPOINTS]
Analysis Window: 28 Days
Analysis Window: 28 Days
Analysis Window: 60 days
Analysis Window: 2 years
[SECONDARY_SUCCESS_ENDPOINTS]
Analysis Window: Up to Day 60
Analysis Window: Up to Day 60
Analysis Window: Up to Day 60
Analysis Window: Up to Day 60
Analysis Window: 1 Year
[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
The maximum-tolerated dose for lintuzumab-Ac225 is defined as the highest level at which no more than one patient experiences a dose-limiting toxicity. The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m\^2/day IV over two hours on days 2-6; cytarabine 2 gm/m\^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m\^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
[DOSING_&_INTERVENTION_SPECIFICITIES]
Lintuzumab-Ac225 is an immunoconjugate \[antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)\] for the treatment of relapsed/refractory acute myeloid leukemia.
Cladribine is a purine antimetabolite.
Cytarabine is an antineoplastic anti-metabolite.
Mitoxantrone is an anthracenedione antineoplastic agent.
G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells.