DFP-10917 + Venetoclax for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Delta-Fly Pharma, Inc.
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: HIV, Hepatitis B/C, CNS leukemia, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, specifically strong or moderate CYP3A inhibitors or inducers, P-gp inhibitors, or narrow therapeutic index P-gp substrates, at least 1 week before starting venetoclax. However, antifungal prophylaxis is allowed.
What data supports the effectiveness of the drug combination DFP-10917 and Venetoclax for treating Acute Myeloid Leukemia?
Research shows that Venetoclax, when combined with other treatments, has been effective for patients with acute myeloid leukemia (AML), especially those who cannot undergo intensive chemotherapy. Clinical trials have demonstrated promising remission and survival rates, making Venetoclax a valuable option in AML treatment.
12345How is the drug DFP-10917 + Venetoclax unique for treating acute myeloid leukemia?
The combination of DFP-10917 and Venetoclax is unique because Venetoclax is a B-cell lymphoma 2 inhibitor that has shown promising results in improving response rates and survival outcomes in acute myeloid leukemia, especially for patients who cannot undergo intensive chemotherapy. This combination may offer a novel approach by potentially enhancing the effectiveness of treatment through different mechanisms of action.
13678Eligibility Criteria
This trial is for adults with Acute Myeloid Leukemia that has come back or didn't respond to previous treatments. Participants must be able to handle continuous IV infusions and oral medications, and have acceptable organ function.Inclusion Criteria
Projected life expectancy of ≥12 weeks
I can take care of myself and perform daily activities.
I agree to use contraception if my partner can become pregnant.
+4 more
Exclusion Criteria
My leukemia has spread to my brain or spinal cord.
I cannot take medications by mouth due to a digestive condition.
I have a history of HIV or active hepatitis B/C.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Phase I
DFP-10917 is administered as a 14-day continuous IV infusion every 28 days, alongside a 14-day oral course of venetoclax following an initial dose ramp-up.
4 weeks per cycle
1 visit (in-person) per cycle
Treatment Phase II
Phase II expansion to assess the treatment's effectiveness against leukemia using a Simon's two-stage design.
4 weeks per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests DFP-10917 given as a continuous IV infusion over 14 days combined with an oral course of venetoclax in patients. The safety and initial effectiveness are evaluated, starting at specific doses which may increase if safe.
2Treatment groups
Experimental Treatment
Group I: DFP-10917 + Venetoclax for 14 daysExperimental Treatment2 Interventions
DFP-10917 4 mg/m\^2/day with venetoclax 400 mg once daily for 14 days
Group II: DFP-10917 + Venetoclax for 10 daysExperimental Treatment2 Interventions
DFP-10917 4 mg/m\^2/day with venetoclax 400 mg once daily for 10 days
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Virginia Cancer CenterCharlottesville, VA
Simmons Cancer Center: UT SouthwesternDallas, TX
UCI Chao Family Comprehensive Cancer CenterOrange, CA
Atrium Health Wake Forest Baptist Comprehensive Cancer CenterWinston-Salem, NC
More Trial Locations
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Who Is Running the Clinical Trial?
Delta-Fly Pharma, Inc.Lead Sponsor
References
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). .
Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? [2020]Venetoclax with backbone therapies have shown promising efficacy for newly diagnosed, previously untreated, older, unfit acute myeloid leukemia patients. This review discusses this data and potential reasons for the efficacy of these venetoclax-based combinations.
A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.
Venetoclax combined with low dose cytarabine compared to standard of care intensive chemotherapy for the treatment of favourable risk adult acute myeloid leukaemia (VICTOR): Study protocol for an international, open-label, multicentre, molecularly-guided randomised, phase II trial. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC.
Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer? [2022]Acute myeloid leukemia (AML) is an aggressive malignancy with poor prognosis and high rates of relapse, especially in elderly patients who are ineligible to receive intensive chemotherapy. Venetoclax, an oral BCL-2 inhibitor, is approved by the Food and Drug Administration in combination with hypomethylating agents or low-dose cytarabine in newly-diagnosed AML patients who are ineligible to receive intensive chemotherapy. Confirmatory phase III VIALE-A and VIALE-C trials showed a composite complete remission rate of 66.4% and 48%, respectively. Thus, further validating venetoclax as an attractive therapeutic option in the AML treatment landscape.
Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy. [2020]Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a globally poor outcome, especially in patients ineligible for intensive chemotherapy. Until recently, therapeutic options for these patients included low-dose cytarabine (LDAC) or the hypomethylating agents (HMA) azacitidine and decitabine, which have historically provided only short-lived and modest benefits. The oral B-cell lymphoma 2 inhibitor, venetoclax, Venetoclax, an oral B-cell lymphoma 2 (BCL2) inhibitor, is now approved by the USA Food and Drug Administration (FDA) in combination with LDAC or HMA in older AML patients ineligible for intensive chemotherapy. Is now approved by the US Food and Drug Administration for this indication. In the pivotal clinical trials evaluating venetoclax either in combination with LDAC or with HMA, the rates of complete remission (CR) plus CR with incomplete hematological recovery were 54% and 67%, respectively and the median overall survival (OS) was 10.4 months and 17.5 months, respectively, comparing favorably with outcomes in clinical trials evaluating single-agent LDAC or HMA. The most common adverse events with venetoclax combinations are gastrointestinal symptoms, which are primarily low grade and easily manageable, and myelosuppression, which may require delays between cycles, granulocyte colony-stimulating factor (G-CSF) administration, or decreased duration of venetoclax administration per cycle. A bone marrow assessment after the first cycle of treatment is critical to determine dosing and timing of subsequent cycles, as most patients will achieve their best response after one cycle. Appropriate prophylactic measures can reduce the risk of venetoclax-induced tumor lysis syndrome. In this review, we present clinical data from the pivotal trials evaluating venetoclax-based combinations in older patients ineligible for intensive chemotherapy, and provide practical recommendations for the prevention and management of adverse events associated with venetoclax.
Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]Venetoclax in combination with nucleoside analogs such as hypomethylating agents (HMA) and low-dose cytarabine (LDAC) has led to unprecedented response and survival outcomes in patients with acute myeloid leukemia (AML). This has spurred the development of regimens combining venetoclax with other nucleoside analogs with distinct mechanisms of action. Here, we review older and newer nucleoside analogs, the rationale for their combination with venetoclax, and clinical evidence for the combination when available.
Outpatient initiation of venetoclax in patients with acute myeloid leukemia. [2023]Venetoclax is a treatment option in patients with acute myeloid leukemia (AML) in both the front-line and relapsed/refractory settings. Initiation of therapy has been previously restricted to the inpatient setting at some institutions due to a risk of tumor lysis syndrome (TLS) and limitations in medication access efficiency given the high cost of therapy.