AZD6738 for Myelodysplastic Syndrome

Recruiting at 3 trial locations

Overseen By Andrew M Brunner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Ataxia telangiectasia, Acute myeloid leukemia, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 4

Duration: 28 days

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a research drug called AZD6738 as a possible treatment for Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia .

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of 5 half-lives for potent inhibitors or inducers of CYP3A4 before starting AZD6738, or three weeks for St. John's Wort. For other medications, the decision will be made on a case-by-case basis with the study doctor.

How is the drug AZD6738 (Ceralasertib) unique for treating myelodysplastic syndrome?

AZD6738 (Ceralasertib) is unique because it targets specific pathways involved in DNA damage response, which is different from other treatments that often focus on inhibiting blood vessel growth or targeting specific mutations. This novel approach may offer a new option for patients with myelodysplastic syndrome who have limited treatment choices. ^{1 2 3 4 5}

Research Team

Andrew M Brunner, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults diagnosed with Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) who have not responded to, or cannot tolerate, certain chemotherapy treatments. They should be in a stable condition without acute leukemia and must not have other active cancers. Participants need functioning major organs and agree to use contraception.

Inclusion Criteria

My MDS or CMML has returned after a stem cell transplant.

Your liver function tests should show AST and ALT levels that are not more than 2.5 times the upper limit of normal.

My MDS or CMML has returned after a stem cell transplant.

Exclusion Criteria

Involvement in the planning and/or conduct of the study

My leukemia has spread to my brain or spinal cord.

I had a transplant less than 100 days ago and am not on strong immune-suppressing drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD6738 orally on a 28-day cycle to evaluate safety, tolerability, and effect on tumor growth

28 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall response rate and survival rates

2 years

Treatment Details

Interventions

• AZD6738

Trial Overview The trial is testing AZD6738, an investigational drug for treating MDS/CMML. It's designed for patients whose disease has progressed after standard therapies or those ineligible for stem cell transplantation. The study will assess the drug's effectiveness and safety.

Participant Groups

Group I: AZD6738 Experimental Treatment 1 Intervention

Patients will receive AZD6738 orally on a 28-day cycle

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a multicenter phase II study involving 39 patients (23 with acute myeloid leukemia and 16 with high-risk myelodysplastic syndrome), the VEGF receptor inhibitor cediranib showed no confirmed responses in treating these conditions, leading to the early closure of the trial.

Despite the lack of efficacy, common adverse events reported included thrombocytopenia, neutropenia, and fatigue, indicating that while the drug was not effective, it did have a safety profile that needs consideration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Mattison, R., Jumonville, A., Flynn, PJ., et al.[2021]

Luspatercept has recently been approved as a targeted therapy for treating anemia in myelodysplastic syndromes (MDS) patients who do not respond to erythropoiesis stimulating agents, marking a significant advancement in treatment options.

Ongoing research is focused on developing new targeted therapies that address myeloid lineage signaling pathways and the immune microenvironment, which could enhance treatment strategies for MDS as current options are limited after treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Myeloid Lineages and the Immune Microenvironment in Myelodysplastic Syndromes: Novel and Evolving Therapeutic Strategies. Chung, C.[2022]

The investigational drug enasidenib, which targets IDH2 mutations, has shown a safety profile and potential to improve survival in patients with relapsed or refractory acute myeloid leukemia.

In a clinical trial, enasidenib induced responses in 40.3% of patients, leading to a median overall survival of 9.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive First Trial of Enasidenib for AML. [2022]

In a study of 155 patients with myelodysplastic syndromes (MDS), vatalanib showed a modest hematological improvement in 5% of patients, with a higher response rate of 15% among those who remained on the treatment for at least 3 months.

While vatalanib delayed progression to acute myeloid leukemia (AML) and improved survival in low-risk patients (median overall survival of 36 months), its clinical use is limited due to significant side effects, including fatigue and nausea, and potential serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance). Gupta, P., Mulkey, F., Hasserjian, RP., et al.[2021]

Enasidenib is a targeted therapy approved by the FDA for patients with refractory or relapsed acute myeloid leukemia (AML) who have a specific mutation (IDH2).

The drug has shown the ability to induce remissions in some patients and may decrease the need for blood transfusions, although its approval was based on less supporting evidence than typically required.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib Approved for AML, but Best Uses Unclear. [2018]

References

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

A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. [2021]

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

Targeting the Myeloid Lineages and the Immune Microenvironment in Myelodysplastic Syndromes: Novel and Evolving Therapeutic Strategies. [2022]

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

Positive First Trial of Enasidenib for AML. [2022]

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

A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance). [2021]

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

Enasidenib Approved for AML, but Best Uses Unclear. [2018]