DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia

NCT06382168 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D19-11186
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (3)

• Number of patients with dose-limiting toxicities assessed by CTCAE v5.0.

  From the first day of treatment start until 30 days after treatment completion.

• Number of patients with treatment-related adverse events assessed by CTCAE v5.0.

  The first 28 days of study treatment (Cycle 1).

• Recommended Phase 2 dose of DFP-10917 in combination with venetoclax (the dose at which <2 out of 6 patients experience a dose-limiting toxicity during the safety assessment period).

  The first 28 days of study treatment (Cycle 1).

Secondary Outcomes (7)

• The proportion of patients who achieve complete remission.

  From the start of the study treatment to the first documented progression or death from any cause, whichever occurs first, assessed for up to 100 months.

• The proportion of patients who achieve complete remission or complete remission with incomplete hematologic recovery.

  From the start of the study treatment to the first documented progression or death from any cause, whichever occurs first, assessed for up to 100 months.

• The proportion of patients achieving complete remission or complete remission with incomplete hematologic recovery, and morphologic leukemia-free state.

  From the start of the study treatment to the first documented progression or death from any cause, whichever occurs first, assessed for up to 100 months.

• Overall survival.

  From the start of the study treatment to death from any cause, whichever occurs first, assessed for up to 100 months.

• Progression-free survival.

  From the start of the study treatment to the first documented progression or death from any cause, whichever occurs first, assessed for up to 100 months.

Other Outcomes (6)

• Volume of distribution of DFP-10917.

  The first 15 days of study treatment.

• Clearance of DFP-10917.

  The first 15 days of study treatment.

• Time to maximum concentration of venetoclax.

  The first 15 days of study treatment.

Study Arms (2)

DFP-10917 + Venetoclax for 14 days

EXPERIMENTAL

DFP-10917 4 mg/m\^2/day with venetoclax 400 mg once daily for 14 days

Drug: DFP-10917; Drug: Venetoclax

DFP-10917 + Venetoclax for 10 days

EXPERIMENTAL

DFP-10917 4 mg/m\^2/day with venetoclax 400 mg once daily for 10 days

Drug: DFP-10917; Drug: Venetoclax

Interventions

DFP-10917 DRUG

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.

DFP-10917 + Venetoclax for 10 days; DFP-10917 + Venetoclax for 14 days

Venetoclax DRUG

Venetoclax 400 mg once daily for 10-14 days, followed by a 14-day rest in each 28-day cycle.

DFP-10917 + Venetoclax for 10 days; DFP-10917 + Venetoclax for 14 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Delta-Fly Pharma, Inc.: lead

Study Sites (4)

UCI Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Vermont Cancer Center

Burlington, Vermont, 05401, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22911, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

DFP-10917; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Scott Frank

CONTACT

+81 362311278; sfrank1206@delta-flypharma.co.jp

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: April 24, 2024
• Study Start: June 12, 2024
• Primary Completion: March 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 3, 2025

Record last verified: 2024-09

Locations

US (4)