DFP-10917 + Venetoclax for Acute Myeloid Leukemia

Recruiting at 4 trial locations

Overseen By Scott Frank

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Delta-Fly Pharma, Inc.

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, CNS leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

39 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{1 3 6 7 8}

Eligibility 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.

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.

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

Treatment Details

Interventions

• DFP-10917
• Venetoclax

Trial Overview 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.

Participant Groups

Group I: DFP-10917 + Venetoclax for 14 days Experimental Treatment 2 Interventions

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

Group II: DFP-10917 + Venetoclax for 10 days Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Delta-Fly Pharma, Inc.

Lead Sponsor

Trials

5

Recruited

610+

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax combined with hypomethylators and low-dose cytarabine has shown high response rates and improved overall survival in older, untreated patients with acute myeloid leukemia, based on preliminary data from small, uncontrolled studies.

The efficacy of venetoclax appears to stem from its ability to target leukemia stem cells by altering the metabolic environment, which is particularly effective in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? Pollyea, DA., Jordan, CT.[2020]

In a study comparing treatment regimens for relapsed/refractory acute myeloid leukemia (R/R AML), the venetoclax (VEN) combination therapy showed a comparable overall response rate (59.3%) to intensive chemotherapy (IC) (44.0%), suggesting it is an effective alternative for patients who have failed previous treatments.

Patients receiving the VEN combination had a significantly higher percentage of successful stem cell transplants at blast clearance (86.5% vs. 62.3% for IC), indicating better disease control and potentially lower treatment-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). Park, S., Kwag, D., Kim, TY., et al.[2022]

Venetoclax combined with low-dose cytarabine (VEN + LDAC) offers a promising low-intensity treatment option for older patients with acute myeloid leukaemia (AML) who cannot tolerate intensive chemotherapy, showing lower toxicity and the potential for comparable remission and survival rates for specific genotypes.

The VICTOR trial is a phase II study designed to assess the effectiveness of VEN + LDAC compared to standard intensive chemotherapy in patients aged 60 and older, with a focus on maintaining quality of life and reducing healthcare costs, while employing an adaptive design to potentially include younger patients if results are favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Dillon, R., Maycock, S., Jackson, A., et al.[2022]

Venetoclax, an oral BCL-2 inhibitor, has shown promising efficacy in treating acute myeloid leukemia (AML) in elderly patients who cannot undergo intensive chemotherapy, with complete remission rates of 66.4% and 48% in phase III trials.

The introduction of venetoclax-based therapies has significantly improved treatment options for these patients, but further studies are needed to evaluate the long-term durability of responses and to explore its effectiveness compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer? Agarwal, S., Kowalski, A., Schiffer, M., et al.[2022]

Venetoclax, an oral BCL2 inhibitor, has been approved for older patients with acute myeloid leukemia (AML) who cannot undergo intensive chemotherapy, showing higher rates of complete remission (54% with LDAC and 67% with HMA) compared to traditional treatments.

The median overall survival for patients treated with venetoclax in combination with LDAC or HMA was significantly improved, at 10.4 months and 17.5 months respectively, while the most common side effects were manageable gastrointestinal symptoms and myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy. Richard-Carpentier, G., DiNardo, CD.[2020]

The combination of venetoclax with hypomethylating agents (HMA) has significantly improved survival rates in patients with acute myeloid leukemia (AML), as demonstrated in a phase 3 study.

Venetoclax is also safe when added to standard intensive regimens, leading to high remission rates and measurable residual disease negativity in both newly diagnosed and relapsed/refractory AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. Ball, BJ., Koller, PB., Pullarkat, V.[2023]

In a study of 82 adult patients with acute myeloid leukemia (AML), 57% were able to start venetoclax treatment safely in an outpatient setting, demonstrating its feasibility outside of the hospital.

The risk of tumor lysis syndrome (TLS) was very low, with only 2.1% of patients experiencing TLS after starting venetoclax, and 98% of patients did not require hospitalization for TLS within the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient initiation of venetoclax in patients with acute myeloid leukemia. Palmer, S., Patel, A., Wang, C., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective? [2020]

3. England pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]

4. England pubmed.ncbi.nlm.nih.gov

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]

5. England pubmed.ncbi.nlm.nih.gov

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]

6. England pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Outpatient initiation of venetoclax in patients with acute myeloid leukemia. [2023]