Trial Title:
Venetoclax + Azacitidine in Patients with Acute Myeloid Leukemia
NCT ID:
NCT06668558
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Venetoclax
Conditions: Keywords:
venetoclax
azacitidine
measurable residual disease (MRD)
allogeneic hematopoietic cell transplantation (alloHCT)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
investigator-initiated, multicenter, multicohort, phase II trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Azacitidine (AZA)
Description:
Dosing is 75 mg/m2 x 7 days (Q28days) After 2 courses, a first decision-making for
allo-HCT based on bone marrow MRD assessment will be performed. After 4th course, a new
MRD assessment will be performed.
For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For
cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)
Arm group label:
Cohort 1
Arm group label:
Cohort 2
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Dosing: 400 mg daily After 2 courses, a first decision-making for allo-HCT based on bone
marrow MRD assessment will be performed. After 4th course, a new MRD assessment will be
performed.
For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For
cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)
Arm group label:
Cohort 1
Arm group label:
Cohort 2
Summary:
The VERDI study is an investigator-initiated, multicenter, multicohort, phase II trial
with combination of venetoclax + azacitidine for patients treated for AML under according
to an intensive chemotherapy protocol (CETLAM-20) failing to achieve or maintain MRD
negativity at pre-established time-points: at chemotherapy completion for ELN favorable
subtypes, and prior to alloHCT for non-favorable European LeukemiaNet (ELN) AML patients.
The primary objective is to determine Ven/Aza treatment activity in MRD clearance in
patients diagnosed with AML with persistent MRD or MRD reappearance after frontline
chemotherapy, or prior to alloHCT.
Detailed description:
The trial will enroll competitively between 25 and 29 patients.
Patients will be recruited in two independent cohorts depending on the pre-established
time point for the intervention and ELN risk subtype:
Cohort 1: Patients diagnosed with a favorable ELN subtype AML, not intended for alloHCT
in first complete remission (CR1), but who present an MRD failure by after frontline
intensive chemotherapy, as defined in the 2021 update on MRD guidelines elaborated by the
European LeukemiaNet MRD Working Party (Heuser et al. 2023):
In patients with persistent low-level MRD (<2%) after consolidation chemotherapy,
an increase of MRD ≥1log10 between 2 positive samples Confirmed MRD conversion of MRD
negativity to MRD positivity AML during subsequent follow-up (up to 3 years after
chemotherapy completion
Cohort 2: Patients diagnosed with a non-favorable ELN AML subtype, intended to undergo
alloHCT, in first complete morphological remission but harboring detectable MRD at time
of alloHCT (>0.1%).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must have confirmation of with acute myeloid leukemia (AML) with persistent
measurable residual disease (MRD) or MRD reappearance after frontline intensive
chemotherapy (including at least one cycle of cytarabine and anthracycline), and
prior to allogeneic hematopoietic cell transplantation (allo-HCT).
1. In patients with NPM1 mutation, qRT-PCR of NPM1 will be the method used to
establish a molecular failure, defined as failure to achieve molecular response
after consolidation therapy (NPM1mut/ABL1·100 > 0.01) or MRD
reappearance after molecular response. All cases of molecular failure must be
confirmed with a second MRD assessment in 2 to 4 weeks.
2. In patients with core-binding factor AML, qRT-BCR of RUNX1-RUNX1T1 and
CBFb-MYH11 transcripts will be used. Patients failing to achieve a major MRD
reduction after consolidation therapy (i.e., RUNX1-RUNX1T1/ABL1·100>0.1
or CBFb-MYH11/ABL1·100>0.1), a log increase in MRD between two positive
samples or confirmed MRD reappearance after molecular response will be
considered as molecular failures and could be included in the trial.
3. In the remaining cases, an appropriate leukemia-associated immunophenotype
(LAIP) measured by multiparameter flow cytometry will be used for MRD
surveillance. A cutoff of 0.1% will be used to define MRD positivity.
2. Age ≥18 years.
3. Without clinical signs of active central nervous system disease.
4. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance status
of ≤2 or Karnofsky performance status (KPS) equivalent.
5. Patients must have adequate renal function as demonstrated by a calculated
creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour
creatinine clearance or by the Cockcroft Gault formula.
6. Patients must have adequate liver function as demonstrated by:
1. aspartate aminotransferase (AST) ≤ 3.0 × upper limit normal (ULN)
2. alanine aminotransferase (ALT) ≤ 3.0 × ULN
3. bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome
7. Non-sterile male patients must use contraceptive methods with partner(s) prior to
beginning study drug administration and continuing up to 3 months after the last
dose of study drug. Male patients must agree to refrain from sperm donation from
initial study drug administration until 3 months after the last dose of study drug.
8. WOCBP must agree to use two reliable forms of contraception simultaneously or to
practice complete abstinence from heterosexual intercourse during the following time
periods related to this study: 1) for at least 28 days before starting therapy; 2)
throughout the entire duration of treatment; 3) during dose interruptions; and 4)
for at least 6 months after discontinuation of therapy (last dose of study drug).
9. Patients must voluntarily sign and date an informed consent, approved by an
Institutional Review Board (IRB), prior to the initiation of any research directed
screening procedures.
Exclusion Criteria:
1. Patient has received other prior rescue treatment for MRD.
2. Patient is known to be positive for Human immunodeficiency virus (HIV). Note: HIV
testing is not required.
3. Patient is known to be positive for hepatitis B (HBV) or C (HCV) infection with the
exception of those with an undetectable viral load.
Note: Hepatitis B or C testing is not required and patients with serologic evidence
of prior vaccination to HBV (i.e., HBsAg-, anti-HBs+ and anti-HBc-) may participate.
4. Patient has known active central nervous system (CNS) involvement from AML.
5. Patient has received within 7 days prior to the first dose of study drug: steroid
therapy ≥ 20 mg/day (prednisone or equivalent) for antineoplastic intent; strong and
moderate CYP3A inhibitors; strong and moderate CYP3A inducers.
6. Patient has consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Star fruit within 3 days prior to the
initiation of study treatment.
7. Patient has any history of clinically significant condition(s) that in the opinion
of the investigator would adversely affect his/her participating in this study
including, but not limited to:
1. New York Heart Association heart failure > class 2.
2. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic,
hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
8. Patient has a malabsorption syndrome or other condition that precludes the enteral
route of administration.
9. Patient exhibits evidence of uncontrolled systemic infection requiring therapy
(viral, bacterial or fungal).
10. Patient has a history of other malignancies within the prior year to study entry,
except for:
1. Adequately treated in situ carcinoma of the breast or cervix uteri.
2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the
skin.
3. Prostate cancer with no plans for therapy of any kind.
4. Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent.
11. Pregnant and breastfeeding females.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Son Espases
Address:
City:
Palma de Mallorca
Zip:
07120
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Son Llatzer
Address:
City:
Palma de Mallorca
Zip:
07198
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Institut Catala D oncologia Badalona
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Del Mar
Address:
City:
Barcelona
Zip:
08003
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital De La Santa Creu I Sant Pau
Address:
City:
Barcelona
Zip:
08025
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Universitari Vall D Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Clinic De Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Institut Catala D oncologia Girona
Address:
City:
Girona
Zip:
17007
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Institut Catala D oncologia Hospitalet
Address:
City:
Hospitalet de Llobregat
Zip:
08908
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida
Address:
City:
Lleida
Zip:
25196
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Universitari Joan XXIII De Tarragona
Address:
City:
Tarragona
Zip:
43005
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Fundacio Assistencial De Mutua De Terrassa
Address:
City:
Terrassa
Zip:
08221
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital General Universitario Gregorio Maranon
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Facility:
Name:
Hospital Clinico Universitario De Valencia
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Contact:
Last name:
A responsible person Designated by the Sponsor
Phone:
0034934344412
Email:
investigacion@mfar.net
Contact backup:
Last name:
A Principal Investigator Designated by th Sponsor, M.D.; Ph.D.
Start date:
October 2024
Completion date:
July 2028
Lead sponsor:
Agency:
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Agency class:
Other
Source:
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06668558
