18 Participants Needed

Selumetinib + Azacitidine for Leukemia

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Overseen ByCancer Clinical Trials Office
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. Treatment will begin within 28 days of screening procedures. Treatment will continue indefinitely, provided that the patient continues to derive benefit. A patient will be taken off study for reasons described in detail in section 3.12 including disease progression, unacceptable toxicity, inter-current illness, withdrawal of consent, or at the discretion of the investigator. Patients will be followed for 12 weeks after the last dose of study drug, until any study treatment related toxicities have stabilized, or until death. The total duration of the study is expected to be approximately 24 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any anti-cancer therapy within 14 days before starting the study, except for hydroxyurea, which can be continued if needed.

What data supports the effectiveness of the drug Azacitidine for leukemia?

Azacitidine has been shown to be effective and safe in treating higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), including in older patients, by prolonging overall survival compared to conventional care. It is recommended as the first-line treatment for most patients with higher-risk MDS.12345

What safety data exists for Azacitidine in humans?

Azacitidine, used for myelodysplastic syndromes and acute myeloid leukemia, has shown adverse events like blood-related issues and infections in clinical trials.678910

What makes the drug Selumetinib + Azacitidine unique for treating leukemia?

The combination of Selumetinib and Azacitidine is unique because it combines a MEK inhibitor (Selumetinib) with a hypomethylating agent (Azacitidine), potentially offering a novel approach to targeting leukemia cells by affecting different pathways involved in cancer cell growth and survival.1351112

Research Team

Olatoyosi Odenike, MD - UChicago Medicine

Olatoyosi M. Odenike

Principal Investigator

University of Chicago

Eligibility Criteria

Adults with high-risk chronic blood cancers like Myeloid Leukemia, who haven't been treated with MEK inhibitors before, can join. They should have certain levels of disease severity and organ function, no recent cancer treatments except possibly hydroxyurea, and not be pregnant or breastfeeding. Participants must use effective birth control.

Inclusion Criteria

My myelofibrosis is high risk, and I can't tolerate or didn't respond to JAK inhibitor therapy.
I can take care of myself and do some daily activities.
My liver tests are within the required range.
See 9 more

Exclusion Criteria

Any uncontrolled concurrent illness that may put the patient at undo risk
Pregnant or lactating patients
I haven't taken any cancer treatments in the last 14 days, except hydroxyurea.
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine subcutaneously on days 1-7 and selumetinib on days 8-21 in 28-day cycles

Indefinite, as long as benefit is derived

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are monitored for long-term outcomes and survival

Up to 100 months

Treatment Details

Interventions

  • Azacitidine
  • Selumetinib
Trial OverviewThe trial is testing the combination of Selumetinib and Azacitidine to find the maximum tolerated dose. It's an early-phase study where patients receive treatment within 28 days after screening and continue indefinitely if beneficial, unless they experience unacceptable side effects or choose to leave.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Azacitidine and selumetinibExperimental Treatment2 Interventions
Subjects will receive azacitidine subcutaneously on days 1-7. Selumetinib will be administered on days 8-21. Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials
1,086
Recruited
844,000+

Findings from Research

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.
Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.
Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia.Meers, S., Selleslag, D., Potier, H., et al.[2018]
In a real-life study of 49 patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), azacitidine demonstrated a clinically acceptable safety profile, with 67.3% of patients experiencing treatment-related adverse events.
Efficacy results showed that 41.4% of MDS and CMML patients achieved a complete or partial response, and 43.8% of transfusion-dependent patients became transfusion-independent, with a median overall survival of 490 days.
Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey.Beguin, Y., Selleslag, D., Meers, S., et al.[2015]
In a phase Ib trial involving 23 patients with newly diagnosed IDH1-mutant acute myeloid leukemia, the combination of ivosidenib and azacitidine resulted in a high overall response rate of 78.3% and a complete remission rate of 60.9%.
The treatment was well tolerated, with a safety profile similar to that of each drug alone, and 71.4% of patients achieving complete remission showed clearance of the mIDH1 mutation in their bone marrow.
Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia.DiNardo, CD., Stein, AS., Stein, EM., et al.[2022]

References

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]
Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. [2015]
Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. [2022]
Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). [2019]
Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. [2022]
Characteristics of adverse event reporting of Xeljanz/Xeljanz XR, Olumiant, and Rinvoq to the US Food and Drug Administration. [2023]
Sunitinib adverse events in metastatic renal cell carcinoma: a meta-analysis. [2021]
A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma. [2022]
Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. [2021]
Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database. [2023]
Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. [2021]
Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia. [2022]