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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with acute myeloid leukemia (a type of blood cancer) that has returned or not responded to other treatments. The study tests the safety and effectiveness of the drugs DFP-10917 (an experimental treatment) and venetoclax when used together. Participants will receive these drugs for either 10 or 14 days as part of the trial. This might suit someone whose leukemia returned or did not improve after up to two other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of DFP-10917 and venetoclax is under study for safety in treating acute myeloid leukemia, particularly when the disease has returned or hasn't responded to previous treatments. Both DFP-10917 and venetoclax have undergone testing in people before, but their combination remains under evaluation.

Participants often experience side effects typical of cancer treatments. A system monitors how people react to the treatment, especially after the first cycle. If side effects, known as dose-limiting toxicities (DLTs), are minimal, it suggests the treatment is relatively well-tolerated, allowing more people to join the study.

Venetoclax is already used for other types of leukemia, providing some confidence about its safety. However, DFP-10917 is still in early testing for this combination, so ongoing studies are crucial to understanding its safety when used with venetoclax. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of DFP-10917 and Venetoclax for treating Acute Myeloid Leukemia (AML) because it offers a novel approach compared to standard therapies like chemotherapy and hypomethylating agents. Unlike these traditional treatments, which often require extended periods to see results and can have significant side effects, this combination works by targeting cancer cells more precisely. DFP-10917 is a new compound that disrupts cancer cell division, while Venetoclax specifically inhibits a protein that helps cancer cells survive. This dual-action approach not only promises to be more effective but also may lead to faster, more noticeable improvements in patients with AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

This trial will evaluate the combination of DFP-10917 and venetoclax for treating acute myeloid leukemia (AML) that has returned or is not responding to treatment. Participants will receive DFP-10917 and venetoclax for either 14 days or 10 days. Research has shown that DFP-10917 disrupts the DNA of cancer cells, potentially stopping their growth, while venetoclax blocks a protein that cancer cells need to survive. Although detailed information from human studies remains limited, early results suggest that these drugs together might be effective. Ongoing studies aim to confirm the effectiveness and safety of this combination for patients. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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]

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 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]

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]

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]

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