Clinical Trials /

Venetoclax and Lintuzumab-Ac225 in AML Patients

NCT03867682

Description:

The study is a multicenter, open label Phase I/II trial. 1. To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapsed/refractory AML. (Phase 1 portion) 2. To assess the percentage of patients with CR, CRh, or Overall Response (CR + CRh), up to 6 months after the start of treatment without receiving other AML therapies. (Phase 2 portion)

Related Conditions:
  • Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Venetoclax and Lintuzumab-Ac225 in AML Patients
  • Official Title: A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML

Clinical Trial IDs

  • ORG STUDY ID: LIN-AC225-AML02
  • NCT ID: NCT03867682

Conditions

  • Acute Myeloid Leukemia
  • Relapsed Adult AML

Interventions

DrugSynonymsArms
Lintuzumab-Ac225ActimabPhase I and Phase II
VenetoclaxVenclextaPhase I and Phase II
SpironolactoneAldactonePhase I and Phase II

Purpose

The study is a multicenter, open label Phase I/II trial. 1. To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapsed/refractory AML. (Phase 1 portion) 2. To assess the percentage of patients with CR, CRh, or Overall Response (CR + CRh), up to 6 months after the start of treatment without receiving other AML therapies. (Phase 2 portion)

Trial Arms

NameTypeDescriptionInterventions
Phase I and Phase IIExperimentalLintuzumab-Ac225 administered on Day 1 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.
  • Lintuzumab-Ac225
  • Venetoclax
  • Spironolactone

Eligibility Criteria

        Inclusion Criteria:

          1. Refractory or relapsed AML which will include:

               1. Refractory disease will be defined as at least 1 prior treatment with no
                  remission.

               2. Relapsed disease will be defined as 5% or more blasts in bone marrow seen after
                  remission.

               3. Patients with AML arising from myelodysplastic syndromes (including CMML) or
                  myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.

          2. Circulating blast count ≤ 200/μL within 10 days prior to first cycle of treatment.
             Hydroxyurea should be used to keep the peripheral blast count ≤ 200/μL until the first
             day of protocol treatment, to the extent that this is possible

          3. ECOG ≤ 2

          4. Estimated creatinine clearance ≥ 50 mL/min

          5. AST and ALT ≤ 3.0 x ULN

          6. Bilirubin ≤ 3.0 x ULN

        Exclusion Criteria:

          1. Active CNS Leukemia.

          2. Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable
             viral load).

          3. Participant has received strong and/or moderate CYP3A inducers within 7 days prior to
             the initiation of study treatment.

          4. Have received prior radiation to maximally tolerated levels to any critical normal
             organ.

          5. Clinically significant cardiac disease.

          6. Active, uncontrolled serious infection.

          7. Have other non-myeloid malignancy within 2 years of entry (with exceptions).

          8. Psychiatric disorder that would preclude study participation

          9. Previous solid organ transplant (prior treatment with SCT is allowed but not if
             patient has GVHD or is still receiving immunosuppression/GVHD therapy).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225
Time Frame:Cycle 1, up to 48 days
Safety Issue:
Description:To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapse/refractory AML.

Secondary Outcome Measures

Measure:Phase I: Overall Response
Time Frame:Up to 6 months
Safety Issue:
Description:Number of patients who's overall response is CR or CRh
Measure:Phase I and II: OS
Time Frame:End of 6 months, 12 months, 2 years
Safety Issue:
Description:Number of patients who died
Measure:Phase I and II: DFS
Time Frame:End of 6 months, 12 months, 2 years
Safety Issue:
Description:Disease-free survival
Measure:Phase I and II: Evaluate incidence of AEs and SAEs
Time Frame:Through study completion, up to 2 years
Safety Issue:
Description:Rate of AEs and SAEs, including infusion-related reactions
Measure:Phase I and II: Evaluate BH3 priming assay results
Time Frame:Completion of Cycle 1, estimated 1 month
Safety Issue:
Description:Summary of assay results
Measure:Phase I and II: MRD status
Time Frame:From date of first dose until the date of first documented response, first assessment at 6 months
Safety Issue:
Description:Number of patients who are MRD negative
Measure:Phase I and II: Lab abnormalities (other than hematologic indices)
Time Frame:Through study completion, up to 2 years
Safety Issue:
Description:Summary of rate of Grade 3/4 lab abnormalities

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Actinium Pharmaceuticals

Trial Keywords

  • Lintuzumab-Ac225
  • Venetoclax
  • Lintuzumab
  • Refractory AML

Last Updated

February 3, 2020