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Drug Interventions

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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients

Clinicaltrials.gov identifier NCT03932318

Recruitment Status Not yet recruiting

First Posted April 30, 2019

Last update posted February 5, 2020

Study Description

Brief summary:

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

  • Condition or Disease:Acute Myeloid Leukemia
    Relapsed Adult AML
  • Intervention/Treatment: Biological: Lintuzumab-Ac225
    Drug: Venetoclax
    Drug: Azacitidine
  • Phase: Phase 1/Phase 2
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • 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 Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
  • Estimated Study Start Date: September 2020
  • Estimated Primary Completion Date: September 2021
  • Estimated Study Completion Date: September 2023
Arms and interventions
Arm Intervention/treatment
Experimental: Phase I and Phase II
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
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.

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.

Drug: Azacitidine
75 mg/m2 will be administered on days 1-7 of a 28-day cycle.
Outcome Measures
  • 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 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML
  • 2. Phase II: Overall Response (CR + CRh + CRi + MLFS) [ Time Frame: Up to 6 months ]
    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
  • Secondary Outcome Measures: 1. Phase I and II: DFS [ Time Frame: Through study completion, up to 2 years ]
    Disease-free survival
  • 2. Phase I: Overall Response [ Time Frame: Up to 6 months ]
    Number of patients who's overall response is CR or CRh or CRi or MLFS
  • 3. Phase I: OS [ Time Frame: Phase I: End of 6 months, 12 months, 24 months. ]
    Number of patients who died
  • 4. Phase II: OS [ Time Frame: Phase II: End of 6 months, 12 months, 24 months ]
    Number of patients who died
  • 5. 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
  • 6. 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
  • 7. Phase I and II: Evaluate BH3 priming assay results [ Time Frame: Completion of Cycle 1, estimated 1 month ]
    Summary of assay results
  • 8. 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
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Histologically confirmed acute myeloid leukemia

2. 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.

3. White blood cell (WBC) count 18 years.

5. Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockroft-Gault formula.

6. AST and ALT ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).

7. Bilirubin ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).

8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

Exclusion Criteria:

1. Have acute promyelocytic leukemia (APL).

2. 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.

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

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

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 as GVHD or is still receiving immunosuppression/GVHD therapy).

Contacts and Locations
Contacts

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

Locations
Sponsors and Collaborators

Actinium Pharmaceuticals

More Information
  • Responsible Party: Actinium Pharmaceuticals
  • ClinicalTrials.gov Identifier: NCT03932318 History of Changes
  • Other Study ID Numbers: LIN-AC225-AML03
  • First Posted: April 30, 2019 Key Record Dates
  • Last Update Posted: February 5, 2020
  • Last Verified: April 2019
  • 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
    Azacitidine
    Lintuzumab
    Refractory AML