Trial Title:
DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia
NCT ID:
NCT06382168
Condition:
Leukemia, Myeloid, Acute
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Venetoclax
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
DFP-10917
Description:
DFP-10917 4 mg/m^2/day is given as a continuous 14-day intravenous infusion, followed by
a 14-day rest in each 28-day cycle.
Arm group label:
DFP-10917 + Venetoclax for 10 days
Arm group label:
DFP-10917 + Venetoclax for 14 days
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Venetoclax 400 mg once daily for 10-14 days, followed by a 14-day rest in each 28-day
cycle.
Arm group label:
DFP-10917 + Venetoclax for 10 days
Arm group label:
DFP-10917 + Venetoclax for 14 days
Summary:
This Phase I/II trial evaluates the safety and preliminary efficacy of DFP-10917 combined
with venetoclax in relapsed or refractory acute myeloid leukemia. DFP-10917 is given as a
14-day continuous IV infusion every 28 days, alongside a 14-day oral course of venetoclax
following an initial dose ramp-up. The initial phase tests a starting dose of 4 mg/m²/day
of DFP-10917 with 400 mg daily of venetoclax. The Data Monitoring Committee reviews
toxicity after one treatment cycle. If DLTs are minimal, more patients are added to
confirm safety. If the lower dose level shows tolerability, it proceeds to the Phase II
expansion to assess the treatment's effectiveness against leukemia using a Simon's
two-stage design, targeting up to 17 participants.
Detailed description:
This study is a Phase I/II, open-label trial exploring dosage and expansion cohorts to
assess the safety and preliminary efficacy of DFP-10917 in combination with venetoclax
for patients with relapsed or refractory acute myeloid leukemia (AML). DFP-10917 will be
administered as a 14-day continuous intravenous infusion starting on Day 1, followed by a
14-day rest period, during each 28-day cycle. This will occur concurrently with
venetoclax, administered orally at a dose of 400 mg daily for 14 days following a dose
ramp-up phase (100 mg and 200 mg on Day 1 and 2, respectively).
In Phase I, the starting dose for DFP-10917 is 4 mg/m²/day, administered concurrently
with 400 mg of venetoclax once daily for 14 days (Dose Level 1). The Data Monitoring
Committee (DMC) will assess dose-limiting toxicities (DLTs) after three patients are
enrolled at this dose level and the last patient has completed the 4-week safety
assessment period (i.e., one cycle of the combination regimen). At Dose Level 1 (4
mg/m²/day of DFP-10917 with venetoclax 400 mg daily for 14 days), if none of the three
patients experience a DLT, the study will enroll an additional three patients at this
dose level to confirm the combination's safety and tolerability. If one out of three
patients experiences a DLT, up to three additional patients may be enrolled. If one or
fewer out of six treated patients experience a DLT at Dose Level 1, this dose will be
declared the recommended Phase II dose (RP2D) and used in the Phase II expansion cohort.
If two or more patients out of the total three to six patients at Dose Level 1 experience
a DLT, the study will continue enrollment at Dose Level 1 (4 mg/m²/day of DFP-10917 for
14 days concurrently with venetoclax 400 mg daily for 10 days of each 28-day cycle) to
determine the safety and tolerability of Dose Level -1. A patient who discontinues
therapy during Cycle 1 without experiencing DLTs is considered evaluable for safety
purposes only if all scheduled doses of DFP-10917 and at least 80% of the venetoclax
doses were administered in the first cycle. Once the RP2D of DFP-10917 in combination
with venetoclax is determined, the expansion cohort will begin enrollment to evaluate the
anti-leukemia efficacy of this combination. A Simon's two-stage min-max design will be
employed, with up to 17 patients expected to participate.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent and ability to comply with protocol requirements.
- Histologically or pathologically confirmed diagnosis of acute myeloid leukemia based
on World Health Organization classification that has relapsed after, or is
refractory to, up to 2 prior induction regimens that may have included intensive
chemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e.,
azacitidine or decitabine with/without venetoclax), or targeted therapy (e.g.,
FLT-3, IDH 1/2, BCL-2, monoclonal antibody).
(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts in
peripheral blood 90 days to 24 months after first complete remission or complete
remission with incomplete hematologic recovery. Refractory acute myeloid leukemia is
defined as persistent disease ≥28 days after initiation of intensive induction therapy
(up to 2 induction cycles) or relapse <90 days after first complete remission or complete
remission with incomplete hematologic recover. Refractory disease for patients undergoing
hypomethylating agent induction is defined as lack of remission following at least 2
cycles of epigenetic therapy without reduction in bone marrow blast status).
- Adequate organ function as defined by the following laboratory values:
- Creatinine clearance >30 mL/min (by Cockcroft-Gault method),
- Total serum bilirubin <1.5 × upper limit of normal unless due to Gilbert's
syndrome, leukemic organ involvement, hemolysis or considered an effect of
regular blood transfusions,
- Alanine aminotransferase and aspartate aminotransferase <3 × upper limit of
normal, unless due to leukemic organ involvement.
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2).
- Projected life expectancy of ≥12 weeks.
- Female patients of childbearing potential must:
- Have a negative serum or urine pregnancy test prior to study treatment
initiation.
- Agree to use at least 1 highly effective form of contraception during study
treatment and for 3 months after the last dose.
- Male patients with female partners of childbearing potential must -- Agree to use at
least 1 highly effective form of contraception during study treatment and for at
least 3 months after the last dose.
Exclusion Criteria:
- Any >Grade 1 persistent clinically significant toxicities from prior chemotherapy.
- Leukemic blast count >25 × 109/L. Hydroxyurea permitted to control leukocytosis.
- Known history of human immunodeficiency virus or active hepatitis B or active
hepatitis C infection.
- Concomitant malignancies for which patients are receiving active therapy at the time
of signing consent. Patients with adequately treated basal or squamous cell
carcinoma of the skin, adequately treated carcinoma in situ (e.g., cervix), breast
cancer receiving adjuvant endocrine therapy or prostate cancer not under active
systemic treatment other than hormonal therapy may enroll irrespective of the time
of diagnosis, with Medical Monitor approval.
- Known active central nervous system involvement by leukemia. Patients with
previously diagnosed central nervous system leukemia are eligible if the central
nervous system leukemia is under control and intrathecal treatment may continue
throughout the study.
- Diagnosis of acute promyelocytic leukemia.
- Prior exposure to anticancer therapies including chemotherapy, radiotherapy or other
investigational therapy, including targeted small molecule agents within 14 days of
the first day of study treatment or within 5 half-lives prior to first dose of study
treatment. Note that hydroxyurea up to 5 g daily × 3 days is permitted to reduce
elevated white blood cell (WBC) count.
- Venetoclax exposure in more than 1 prior regimen.
- Prior exposure to biologic agents (e.g., monoclonal antibodies) for anti-neoplastic
intent within 14 days prior to first dose of study drug.
- Prior hematopoietic stem cell transplantation.
- Malabsorption syndrome or other condition that precludes enteral route of
administration.
- Pregnancy or lactation.
- Active uncontrolled systemic infection (viral, bacterial, or fungal).
- Ongoing treatment with strong or moderate CYP3A inhibitors or CYP3A inducers, P-gp
inhibitors, or narrow therapeutic index P-gp substrates that cannot be discontinued
at least 1 week prior to start of venetoclax dosing excluding antifungal
prophylaxis.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCI Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kiran Naqvi, MD, MPH
Phone:
714-456-8000
Email:
knaqvi1@hs.uci.edu
Investigator:
Last name:
Kiran Naqvi, MD, MPH
Email:
Principal Investigator
Facility:
Name:
Atrium Health Wake Forest Baptist Comprehensive Cancer Center
Address:
City:
Winston-Salem
Zip:
27157
Country:
United States
Status:
Recruiting
Contact:
Last name:
Timothy Pardee, MD
Phone:
336-716-5847
Email:
tspardee@wakehealth.edu
Investigator:
Last name:
Timothy Pardee
Email:
Principal Investigator
Facility:
Name:
University of Vermont Cancer Center
Address:
City:
Burlington
Zip:
05401
Country:
United States
Status:
Recruiting
Contact:
Last name:
Diego Adrianzen Herrera, MD
Phone:
802-656-2021
Email:
dadrianz@med.uvm.edu
Investigator:
Last name:
Diego Adrianzen Herrer
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22911
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michael Keng, MD
Phone:
434-424-1505
Email:
mk2pv@uvahealth.org
Investigator:
Last name:
Michael Keng
Email:
Principal Investigator
Start date:
June 12, 2024
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Delta-Fly Pharma, Inc.
Agency class:
Industry
Source:
Delta-Fly Pharma, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06382168
