Trial Title:
BCL2i CLAG-M in R/R Acute Myeloid Leukemia
NCT ID:
NCT06660368
Condition:
Relapsed or Refractory Acute Myeloid Leukemia (AML)
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Venetoclax
Mitoxantrone
Cladribine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen
Description:
Filgrastim/G-CSF 300 mcg/day for 6 days beginning 24 hours prior to multiagent
chemotherapy (days 0-5), cladribine 5 mg/m2 given intravenously over 2 hours for 5
consecutive days (days 1-5), cytarabine given IV over 4 hours for 5 consecutive days
(days 1-5) beginning 2 hours after the completion of cladribine, and mitoxantrone 16
mg/m2 given intravenously over 30 minutes for 3 days (days 1-3) after completion of
cytarabine.
Arm group label:
CLAG-based therapy with venetoclax
Arm group label:
CLAG-based therapy without venetoclax
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Venetoclax will be administered orally, once daily, with food.
Arm group label:
CLAG-based therapy with venetoclax
Summary:
This multicenter, open-label phase II study combines CLAG-based therapy with or without
venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) in
order to improve measurable residual disease (MRD) clearance and event-free survival.
Investigators hypothesize that the addition of venetoclax to CLAG-M in patients with
relapsed or refractory AML is safe, and superior to CLAG-M alone in improving patient
outcomes.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Provision of signed and dated informed consent form.
- Ability to understand and stated willingness to comply with all study procedures and
availability for the duration of the study.
- Adults aged ≥18 years - 80 years.
- Patients with documented refractory or relapsed AML: Refractory disease is defined
as failure to achieve CR (i.e., <5% blasts in BM or blood) with or without normal
restoration of hematopoiesis (Cri) after at least 1 cycle of intensive induction
therapy (or 2 cycles of non-intensive induction). Relapse: Recurrence of disease
after achieving remission, meeting one or more of the following criteria: ≥ 5%
blasts in the marrow or peripheral blood, extramedullary disease.
- Secondary AML arising out of MDS previously treated with HMA, HMA + venetoclax (if >
3 months from venetoclax exposure), and/or 1 cycle of induction chemotherapy.
- Extramedullary AML with marrow involvement is allowed as long as concurrent
medullary AML is present.
- ECOG performance status ≤ 2.
- Participants must have adequate organ function as defined within the protocol.
- Human immunodeficiency virus (HIV)-infected participants on effective
anti-retroviral therapy with undetectable viral load within 6 months are eligible
for this trial. Testing is not mandatory.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and have an undetectable HCV viral load. For participants with HCV infection
who are currently on treatment, they are eligible if they have an undetectable HCV
viral load. Testing is not mandatory.
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation and for 4 months after completion of study drug
administration.
Exclusion Criteria:
- Venetoclax-refractory disease or recent venetoclax exposure < 3 months prior to
first dose of study therapy.
- Prior treatment with a high-dose cytarabine-containing regimen (e.g., no prior
CLAG/FLAG/MEC/CLIA/HAM, etc.).
- Allogeneic stem cell transplant in the past 3 months.
- Less than 14 days from last AML-directed therapy or five half-lives, whichever is
shorter, not including hydroxyurea.
- Known history of prior TP53 mutation (results from any myeloid mutation panel are
not required for screening eligibility).
- Active CNS involvement by AML.
- WBC count ≥25k at the time study treatment begins.
- Uncontrolled intercurrent systemic illness that would limit compliance.
- Concurrent malignancy in addition to AML that requires active treatment with some
exceptions.
- Immunosuppressive therapy in the past 14 days except for prednisone at ≤ 10 mg/day
or equivalent AND no active or uncontrolled graft-versus-host disease (GvHD).
- Participants who have not recovered from adverse events (Aes) due to prior
anti-cancer therapy (i.e., have residual toxicities > Grade 1), with the exception
of alopecia.
- Participants who are receiving any other investigational agents.
- Participants with psychiatric illness/social situations that would limit compliance
with study requirements.
- Patients with active heart disease that limits the use of mitoxantrone or recent (<6
months) history of an acute cardiovascular event (STEMI, NSTEMI).
- Pregnant women are excluded from this study because venetoclax, cladribine, and
cytarabine are agents with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with these drugs, breastfeeding should be
discontinued.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Contact:
Last name:
Chelsea Conner
Phone:
813-745-1359
Email:
Chelsea.Conner@moffitt.org
Contact backup:
Last name:
David Sallman, MD
Contact backup:
Last name:
Onyee Chan, MD
Contact backup:
Last name:
Rami Komrokji, MD
Contact backup:
Last name:
Timothy Kubal, MD
Contact backup:
Last name:
Jeffrey Lancet, MD
Contact backup:
Last name:
Eric Padron, MD
Contact backup:
Last name:
Alison Walker, MD
Contact backup:
Last name:
Zoey Xie, MD
Contact backup:
Last name:
Seongseok Yun, MD, PhD
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Contact:
Last name:
Jacqueline Garcia, MD
Phone:
617-632-1906
Email:
jacqueline_garcia@dfci.harvard.edu
Contact backup:
Last name:
Jacqueline Garcia, MD
Start date:
November 2024
Completion date:
November 2027
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
AbbVie
Agency class:
Industry
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06660368
