Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients

NCT03932318 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: LIN-AC225-AML03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is a multicenter, open label Phase I/II trial.

1. 1.To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML. (Phase I portion)
2. 2.To assess the percentage of patients with CR, CRh, CRi, MLFS or Overall Response (CR + CRh + CRi + MLFS), up to 6 months after the start of treatment without receiving other AML therapies.. (Phase 2 portion)

Conditions

Acute Myeloid Leukemia; Relapsed Adult AML

Keywords

Lintuzumab-Ac225; Venetoclax; Azacitidine; Lintuzumab; Refractory AML

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225

  To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML

  Cycle 1, up to 48 days

• Phase II: Overall Response (CR + CRh + CRi + MLFS)

  To assess the percentage of patients achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS), or Overall Response (CR + CRh + CRi + MLFS), up to 6 months after the start of treatment without receiving other AML therapies

  Up to 6 months

Secondary Outcomes (8)

• Phase I: Overall Response

  Up to 6 months

• Phase I: OS

  Phase I: End of 6 months, 12 months, 24 months.

• Phase II: OS

  Phase II: End of 6 months, 12 months, 24 months

• Phase I and II: DFS

  Through study completion, up to 2 years

• Phase I and II: Evaluate incidence of AEs and SAEs

  Through study completion, up to 2 years

Study Arms (1)

Phase I and Phase II

EXPERIMENTAL

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.

Biological: Lintuzumab-Ac225; Drug: Venetoclax; Drug: Azacitidine

Interventions

Lintuzumab-Ac225 BIOLOGICAL

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.

Also known as: Actimab

Phase I and Phase II

Venetoclax DRUG

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.

Also known as: Venclexta

Phase I and Phase II

Azacitidine DRUG

75 mg/m2 will be administered on days 1-7 of a 28-day cycle.

Also known as: Vidaza

Phase I and Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed acute myeloid leukemia
• Refractory or relapsed AML which will include:
• Refractory disease will be defined as at least 1 prior treatment with no remission.
• Relapsed disease will be defined as 5% or more blasts in bone marrow seen after remission.
• Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.
• White blood cell (WBC) count \< 10 x 109/L;
• a. Use of hydroxyurea, prior to Cycle 1 and during Cycles 1 and 2, is permitted to lower the WBC count in the peripheral blood.
• Age \> 18 years.
• Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockroft-Gault formula.
• AST and ALT ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
• Bilirubin ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

You may not qualify if:

• Have acute promyelocytic leukemia (APL).
• Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
• Have received prior radiation to maximally tolerated levels to any critical normal organ.
• Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
• Clinically significant cardiac disease.
• Active, uncontrolled serious infection.
• Have other non-myeloid malignancy within 2 years of entry (with exceptions).
• Psychiatric disorder that would preclude study participation
• Previous solid organ transplant (prior treatment with SCT is allowed but not if patient as GVHD or is still receiving immunosuppression/GVHD therapy).

Sponsors & Collaborators

• Actinium Pharmaceuticals: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Avinash Desai, MD

  Actinium Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: April 30, 2019
• Study Start: March 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: September 1, 2024
• Last Updated: July 20, 2023

Record last verified: 2023-07