Combining DFP-10917 with Venetoclax for treating relapsed or refractory acute myeloid leukemia

Phase I/II Study of DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia

This study is testing a new combination of two drugs, DFP-10917 and venetoclax, to see if they can help people with relapsed or refractory acute myeloid leukemia feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Delta-Fly Pharma, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 4 sites (Orange, California and 3 other locations)
• Trial ID: NCT06382168 on ClinicalTrials.gov

What this trial studies

This Phase I/II trial evaluates the safety and preliminary efficacy of DFP-10917 in combination with venetoclax for patients with relapsed or refractory acute myeloid leukemia (AML). DFP-10917 is administered as a continuous intravenous infusion over 14 days, while venetoclax is given orally for 14 days following a dose ramp-up. The study begins with a starting dose of 4 mg/m²/day of DFP-10917 and 400 mg of venetoclax daily, with a Data Monitoring Committee assessing toxicity after the first treatment cycle. If the treatment is well-tolerated, the study will expand to further evaluate its effectiveness against AML.

Who should consider this trial

Good fit: Ideal candidates include individuals with histologically confirmed relapsed or refractory acute myeloid leukemia who have undergone up to two prior induction regimens.

Not a fit: Patients who have not been diagnosed with acute myeloid leukemia or those who have not relapsed or are refractory to previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat acute myeloid leukemia.

How similar studies have performed: Other studies have shown promise with similar combinations of targeted therapies in treating acute myeloid leukemia, suggesting potential for success in this approach.

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.

Where this trial is running

Orange, California and 3 other locations

• UCI Chao Family Comprehensive Cancer Center — Orange, California, United States (Recruiting)
• Atrium Health Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem, North Carolina, United States (Recruiting)
• University of Vermont Cancer Center — Burlington, Vermont, United States (Recruiting)
• University of Virginia Cancer Center — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Scott Frank

Conditions Leukemia, Myeloid, Acute