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Trial record 4 of 160 for:    Venetoclax AND overall

Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients

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ClinicalTrials.gov Identifier: NCT03932318
Recruitment Status : Not yet recruiting
First Posted : April 30, 2019
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Actinium Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 17, 2019
First Posted Date  ICMJE April 30, 2019
Last Update Posted Date April 30, 2019
Estimated Study Start Date  ICMJE July 2019
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • 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
  • Phase I: OS [ Time Frame: Phase I: End of 6 months, 12 months, 24 months. ]
    Number of patients who died
  • Phase II: OS [ Time Frame: Phase II: End of 6 months, 12 months, 24 months ]
    Number of patients who died
  • Phase I and II: DFS [ Time Frame: Through study completion, up to 2 years ]
    Disease-free survival
  • 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
  • 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
  • Phase I and II: Evaluate BH3 priming assay results [ Time Frame: Completion of Cycle 1, estimated 1 month ]
    Summary of assay results
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients
Official Title  ICMJE A Phase I/II Study of Venetoclax and Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
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)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Relapsed Adult AML
Intervention  ICMJE
  • 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: Azacitidine
    75 mg/m2 will be administered on days 1-7 of a 28-day cycle.
    Other Name: Vidaza
Study Arms  ICMJE 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.

Interventions:
  • Biological: Lintuzumab-Ac225
  • Drug: Venetoclax
  • Drug: Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
38
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 < 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.

  4. Age > 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Actinium Pharmaceuticals, Inc. +1-646-677-3878 actimab@actiniumpharma.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03932318
Other Study ID Numbers  ICMJE LIN-AC225-AML03
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actinium Pharmaceuticals
Study Sponsor  ICMJE Actinium Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Actinium Pharmaceuticals
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP