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Venetoclax and Lintuzumab-Ac225 in AML Patients

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ClinicalTrials.gov Identifier: NCT03867682
Recruitment Status : Not yet recruiting
First Posted : March 8, 2019
Last Update Posted : November 29, 2019
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals

Study Description
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Brief Summary:

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)

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Relapsed Adult AML Biological: Lintuzumab-Ac225 Drug: Venetoclax Drug: Spironolactone Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase I and Phase II

Lintuzumab-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.

 Biological: Lintuzumab-Ac225
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.
Other Name: Actimab

Drug: Venetoclax
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.
Other Name: Venclexta

Drug: Spironolactone
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.
Other Name: Aldactone


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

  2. Phase II: Overall Response (CR + CRh) [ Time Frame: Up to 6 months ]
    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.


Secondary Outcome Measures :
  1. Phase I: Overall Response [ Time Frame: Up to 6 months ]
    Number of patients who's overall response is CR or CRh

  2. Phase I and II: OS [ Time Frame: End of 6 months, 12 months, 2 years ]
    Number of patients who died

  3. Phase I and II: DFS [ Time Frame: End of 6 months, 12 months, 2 years ]
    Disease-free survival

  4. Phase I and II: Evaluate incidence of AEs and SAEs [ Time Frame: Through study completion, up to 2 years ]
    Rate of AEs and SAEs, including infusion-related reactions

  5. Phase I and II: Evaluate BH3 priming assay results [ Time Frame: Completion of Cycle 1, estimated 1 month ]
    Summary of assay results

  6. 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 ]
    Number of patients who are MRD negative

  7. Phase I and II: Lab abnormalities (other than hematologic indices) [ Time Frame: Through study completion, up to 2 years ]
    Summary of rate of Grade 3/4 lab abnormalities


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03867682


Contacts
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Contact: Actinium Pharmaceuticals, Inc. +1-646-677-3878 actimab@actiniumpharma.com

Sponsors and Collaborators
Actinium Pharmaceuticals
More Information
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Responsible Party: Actinium Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03867682    
Other Study ID Numbers: LIN-AC225-AML02
First Posted: March 8, 2019    Key Record Dates
Last Update Posted: November 29, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Actinium Pharmaceuticals:
Lintuzumab-Ac225
Venetoclax
Lintuzumab
Refractory AML
Additional relevant MeSH terms:
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Venetoclax
Lintuzumab
Spironolactone
Antineoplastic Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
 Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antineoplastic Agents, Immunological