40 Participants Needed

Nadunolimab + Azacitidine for Preleukemia and Acute Myeloid Leukemia

GB
Overseen ByGautam Borthakur, MBBS
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but you cannot use chemotherapeutic or anti-leukemic agents during the study, except for certain cases like intrathecal therapy or specific doses of cytarabine and hydroxyurea. There is a 7-day washout period for cytarabine before starting the study therapy.

What data supports the effectiveness of the drug combination of Nadunolimab, Azacitidine, and Venetoclax for preleukemia and acute myeloid leukemia?

Research shows that combining venetoclax with azacitidine improves remission rates and survival in patients with acute myeloid leukemia compared to azacitidine alone. This suggests that the combination of these drugs could be effective for treating similar conditions.12345

Is the combination of Nadunolimab and Azacitidine safe for humans?

The combination of venetoclax and azacitidine, which is similar to Nadunolimab and Azacitidine, has been studied in patients with acute myeloid leukemia and is generally considered to have acceptable safety. Common side effects include blood-related issues and gastrointestinal problems, but the treatment is usually tolerable for patients.36789

What makes the drug combination of Nadunolimab, Azacitidine, and Venetoclax unique for treating preleukemia and acute myeloid leukemia?

This drug combination is unique because it includes Nadunolimab, which is not commonly used in standard treatments for acute myeloid leukemia. The addition of Nadunolimab to the established combination of Azacitidine and Venetoclax may offer a novel approach to improve treatment outcomes for patients with preleukemia and acute myeloid leukemia.12346

What is the purpose of this trial?

To evaluate safety and determine the recommended Phase II dose (RP2D). We hypothesize that targeting leukemia stem/progenitor cells (LSCs) with nadunolimab (IL1RAP antibody) alone or in combination with current therapies of azacitidine (HMA) and venetoclax (Bcl-2 inhibitor), is an effective treatment strategy for high-risk MDS and AML, and with a clinical trial we will establish the safety and the early efficacy of this approach.

Research Team

Gautam Borthakur | MD Anderson Cancer ...

Gautam Borthakur, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with high-risk Myelodysplastic Syndrome (MDS) or Acute Myelogenous Leukemia (AML). Participants should not have received certain prior treatments and must meet specific health conditions. Detailed inclusion and exclusion criteria are provided to determine eligibility.

Inclusion Criteria

Serum biochemical values within specified limits
I am sterile or agree to use contraception.
I've had temporary treatments like apheresis or low-dose cytarabine, but not as part of my main cancer therapy.
See 10 more

Exclusion Criteria

I do not have any severe or uncontrolled medical conditions.
I am willing and able to follow the study rules.
I have not received a live vaccine in the last 28 days.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nadunolimab in combination with azacitidine, with or without venetoclax, for up to 24 cycles

24 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Azacitidine
  • Nadunolimab
  • Venetoclax
Trial Overview The trial tests the safety and optimal dose of Nadunolimab, alone or combined with Azacitidine and/or Venetoclax, in treating MDS/AML. It aims to see if targeting leukemia stem cells with this combination can be an effective treatment strategy.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: ARM 2: Relapsed/refractory AMLExperimental Treatment3 Interventions
Group II: ARM 1B: Cycle 2-24 for non responder after Cycle 1 ComboExperimental Treatment3 Interventions
Group III: ARM 1A: Cycle 2-24 for responder after Cycle 1 MonoExperimental Treatment3 Interventions
Group IV: ARM 1: All Patients Cycle 1Experimental Treatment1 Intervention

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

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Approved in European Union as Vidaza for:
  • Acute myeloid leukemia
  • Chronic myelomonocytic leukemia
  • Myelodysplastic syndromes
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Approved in United States as Vidaza for:
  • Myelodysplastic syndromes
  • Chronic myelomonocytic leukemia
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Approved in Canada as Vidaza for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia
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Approved in Japan as Vidaza for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

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.
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 a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.
The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy.Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]
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.
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-SokoΕ‚owska, J., MΔ…dry, K., Barankiewicz, J., et al.[2023]

References

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]
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]
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]
Azacitidine-venetoclax versus azacitidine salvage treatment for primary induction failure or first relapsed acute myeloid leukaemia patients. [2023]
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]
[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022]
Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]
Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. [2023]
Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. [2023]
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