DSP107 + Azacitidine/Venetoclax for Leukemia

Recruiting at 1 trial location

Overseen By Yaffa Shwartz

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kahr Medical

Must be taking: Azacitidine, Venetoclax

Must not be taking: Immunostimulatory, CD47/SIRPα agents

Disqualifiers: Autoimmune disease, CNS leukemia, others

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

Compensation: Varies

Number of Visits: 214

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will be divided into two parts, Parts A and B and will enroll patients with relapsed/refractory AML or MDS/chronic myelomonocytic leukemia (CMML) patients who have failed up to 2 prior therapeutic regimens. Part A is a dose escalation study to explore the safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) profile of DSP107 when administered in combination with azacitidine (AZA). Part B is a dose escalation study to explore the safety, efficacy, PK and PD profile of DSP107 when administered in combination with AZA and venetoclax (VEN).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments, like systemic immunostimulatory drugs, within 4 weeks before starting the study.

What data supports the effectiveness of the drug combination DSP107 + Azacitidine/Venetoclax for treating leukemia?

Research shows that the combination of venetoclax and azacitidine improves remission rates and survival in older or unfit patients with acute myeloid leukemia compared to azacitidine alone. Additionally, venetoclax combined with azacitidine or low-dose cytarabine is associated with lower costs per patient achieving remission compared to azacitidine alone. ^{1 2 3 4 5}

Is the combination of DSP107, Azacitidine, and Venetoclax safe for humans?

The combination of Venetoclax and Azacitidine has been studied in patients with acute myeloid leukemia, showing common side effects like blood-related issues and stomach problems. However, it is generally considered safe and feasible, even in outpatient settings, with careful monitoring. ^{4 6 7 8 9}

What makes the drug combination of DSP107, Azacitidine, and Venetoclax unique for treating leukemia?

The combination of DSP107 with Azacitidine and Venetoclax is unique because it introduces DSP107, a novel component, to the existing regimen of Azacitidine and Venetoclax, which is already used for treating acute myeloid leukemia in patients who cannot undergo intensive chemotherapy. This new combination may offer a different mechanism of action or improved outcomes, although specific details about DSP107's role are not provided in the available research. ^{1 2 4 5 6}

Eligibility Criteria

This trial is for patients with certain blood cancers like AML, MDS, or CMML who have tried and failed up to two treatments. They should have a white blood cell count under a specific limit, decent organ function, and be in fair to good physical condition (ECOG 0-2). It's not for those with severe liver disease, recent immunostimulatory treatment, active hepatitis B or C infection, lung issues, pregnancy/breastfeeding intentions during the study period.

Inclusion Criteria

My AML or MDS/CMML has not improved after up to 2 treatments.

I can take care of myself and am up and about more than 50% of my waking hours.

White Blood Cell count < 20 x 10^9/L

Exclusion Criteria

I have not been treated with drugs targeting CD47/SIRPα or immune boosters.

I have not received a live vaccine in the last 4 weeks.

I do not have any uncontrolled health conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Dose escalation study to explore the safety, efficacy, PK, and PD profile of DSP107 in combination with azacitidine (AZA).

28 days per cycle

Weekly visits for DSP107 infusion

Treatment Part B

Dose escalation study to explore the safety, efficacy, PK, and PD profile of DSP107 in combination with AZA and venetoclax (VEN).

28 days per cycle

Weekly visits for DSP107 infusion, daily dose escalation for venetoclax in Cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Azacitidine
• DSP107
• Venetoclax

Trial Overview The trial tests DSP107 combined with azacitidine (AZA) in Part A and adds venetoclax (VEN) in Part B. Both parts aim to find safe doses while checking how well these combinations work against the cancer by monitoring their effects on the body and cancer cells.

Participant Groups

Group I: DSP107 in combination with azacitidine or azacitidine plus venetoclax. Experimental Treatment 3 Interventions

DSP107 will be administered by intravenous infusion once weekly during each 28-day cycle to all patients in this study. Azacitidine (75 mg/m2/day) will be administered subcutaneously or intravenously for the first 7 days of every cycle. Patients enrolled in Part B only will also receive venetoclax. During Cycle 1, venetoclax will be dose escalated daily to the goal dose of 400 mg daily. Patients will receive 100 mg on Day 1, 200 mg on Day 2 and 400 mg on Day 3 and onwards.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Kahr Medical

Lead Sponsor

Trials

3

Recruited

160+

Findings from Research

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

Venetoclax combined with azacitidine or low-dose cytarabine (LDAC) is associated with significantly lower costs per patient achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) compared to other treatments for newly diagnosed acute myeloid leukemia (AML) patients who cannot undergo intensive chemotherapy.

The estimated costs per patient achieving CR + CRi were $473,960 for venetoclax + azacitidine and $428,071 for venetoclax + LDAC, which are substantially lower than the costs for azacitidine ($1,197,438) and other therapies, indicating a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy. Choi, M., Song, J., Bui, CN., et al.[2022]

In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.

The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. Drozd-Sokołowska, J., Mądry, K., Barankiewicz, J., et al.[2023]

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In a study of 57 elderly patients (average age 69.9 years) with acute myeloid leukemia, the combination of venetoclax and azacitidine (VEN + AZA) showed a high overall response rate of 87.5% and a complete remission (CR) rate of 68.8%, indicating strong efficacy in this population.

The treatment was associated with a median overall survival (OS) of 11.5 months, and achieving minimal residual disease (MRD) negativity (<0.1%) was more common with VEN + AZA compared to traditional chemotherapy, although older patients (≥75 years) and those with higher ECOG scores faced more challenges in achieving MRD negativity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. Yu, H., Wang, C., Lei, Y., et al.[2023]

Outpatient induction therapy using low-dose venetoclax combined with itraconazole and azacitidine is feasible and safe for newly diagnosed acute myeloid leukemia (ND-AML) patients, with 77.7% of participants completing the first treatment cycle as outpatients.

The treatment showed promising efficacy, with a composite complete response rate of 53.9% after the first cycle and 85.7% after the second cycle, indicating that this regimen could be a viable option for patients eligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. De la Garza-Salazar, F., Colunga-Pedraza, PR., Gómez-Almaguer, D., et al.[2023]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

References

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

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. [2023]

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

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. [2023]

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

TP53 or Not TP53: That Is the Question. [2023]

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

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. [2023]

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

Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]