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Venetoclax and Decitabine Assessment in Patients (≥60 - <75 Years) With Newly Diagnosed AML Eligible for Allo-SCT

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ClinicalTrials.gov Identifier: NCT04476199
Recruitment Status : Not yet recruiting
First Posted : July 20, 2020
Last Update Posted : March 18, 2021
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Trapianto di Midollo Osseo

Brief Summary:
This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the safety and efficacy of the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) as "bridge" to allo-SCT in elderly (≥ 60 - < 75 years) AML patients. The primary objective is to evaluate the proportion of elderly (≥60 - <75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/Cri/MLFS.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Combination Product: Venetoclax and Decitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: These patients may undergo allo-SCT after 2 - 4 cycles of VEN-DEC
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study on Venetoclax (VEN) Plus Decitabine (DEC) (VEN-DEC) for Elderly (≥60 <75years) Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Elegible for Allogeneic Stem Cell Transplantation (Allo-SCT)
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : June 2024


Arm Intervention/treatment
Experimental: Treatment with VEN-DEC
Venetoclax will be given with a 3-day ramp up beginning with 100 mg dose on Day 1, with 200mg on Day 2, to reach the final dose of 400 mg on Day 3 of Cycle 1. Venetoclax will be continued at 400 mg daily. Tumor lysis prophylaxis will be administered from day -4, cycle 1 (oral uric acid reducing agent and hydration with at least 1.5 L/day).Decitabine will be administered at the dose of 20 mg/sqm intravenously from day 1 to day 5 every 28 days (VEN-DEC) for 2 cycles.
Combination Product: Venetoclax and Decitabine
The prognosis of acute myeloid leukemia (AML) patients aged over 60 years is poor and allogeneic stem cell transplantation (allo-SCT) is the only curative option.The association VEN-DEC is a promising combination therapy for AML elderly patients who are fit and eligible for allo-SCT.




Primary Outcome Measures :
  1. Response to VEN-DEC chemo-free combination (ELN Guidelines) [ Time Frame: At the end of cycle 2 (each cycle is 28 days) ]
    response to VEN-DEC induction will be assessed on bone marrow according to the ELN Guidelines (13), as following: - CR without minimal residual disease (CR-MRD neg); (Complete Remission ) bone marrow blasts 5%) - CR remission with incomplete hematologic recovery (CRi): Morphologic Leukemia-free State (MLFS) Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%; - Primary refractory disease/Non response (NR): No CR or CRi after 2 courses of VEN-DEC; excluding patients with death in aplasia or death due to indeterminate cause;

  2. Allo-SCT [ Time Frame: 18 months from 1st enrolled patient ]
    Proportion of patients who undergo to allo-SCT in first CR/CRi/MLFS

  3. Allo-SCT Engraftment [ Time Frame: up to 24 weeks ]
    Percentage of patients with Neutrophil engraftment and percentage of patients with platelet engraftment

  4. Overall Survival (OS) [ Time Frame: at 2 year post transplant ]
    at 2 year post transplant. OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis

  5. Cumulative incidence of Non-Relapse Mortality [ Time Frame: at 100 days ]
    NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 100 days

  6. Cumulative incidence of Non-Relapse Mortality [ Time Frame: at 180 days ]
    NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 180 days

  7. Cumulative incidence of Non-Relapse Mortality [ Time Frame: at 365 days ]
    NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 365 days



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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • Patients >60 <75 years of age

    • Diagnosis of AML eligible for allo-SCT from any donor
    • High- and Intermediate-Risk ELN
    • WBC <25x109/L (Hydroxyurea is permitted to meet this criterion)
    • adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL)
    • adequate renal function (creatinine clearance ≥50 ml/min)
    • ECOG Performance Status < 2
    • Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial.
    • Women of childbearing potential must use highly effective contraception for at least 1 month after the last dose of VEN and for however long the EU SmPC says for DEC
    • Willing and able to comply with all of the requirements and visits in the protocol.
    • Written and signed informed consent.

Exclusion Criteria:

  • • Previous treatment for AML (Hydroxyurea is allowed) or for an antecedent Myelodysplastic Syndrome (MDS).

    • Absence of informed consent
    • AML patients with t(15;17); t(8;21); inv(16)
    • Subject has known active CNS involvement with AML.
    • Low Risk ELN
    • grade >2 NCI-CTCAE (v. 5) adverse events at the time of enrollment
    • Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) <40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min.
    • The evidence of HBV or HCV active infection (HBV DNA HCV RNA positive test).
    • Patients with HIV infection
    • Current uncontrolled infections
    • Patients with other life-threatening concurrent disease
    • Subjects with known hypersensitivity to any of the component medication
    • Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. • Participation in another clinical trial within 1 month before the start of this trial

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): NCT04476199


Contacts
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Contact: Massimo Martino, MD 00393343293566 dr.massimomartino@gmail.com
Contact: Angela Gheorghiu 00393783012898 segreteria.presidenza@gitmo.it

Locations
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Sponsors and Collaborators
Gruppo Italiano Trapianto di Midollo Osseo
Investigators
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Principal Investigator: Domenico Russo, MD Spedali Civili Brescia
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Responsible Party: Gruppo Italiano Trapianto di Midollo Osseo
ClinicalTrials.gov Identifier: NCT04476199    
Other Study ID Numbers: GITMO-VEN-DEC
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: March 18, 2021
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Trapianto di Midollo Osseo:
Acute Myeloid Leukemia
Allogenic Stem Cell Transplant
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Decitabine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors