Guadecitabine + Atezolizumab for Chronic Myelomonocytic Leukemia

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Southern California

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Autoimmune disease, Lung disease, AML, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

33 Participants Needed

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 your current medications. However, you cannot be on other anticancer therapies or certain immunosuppressive medications before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drugs Guadecitabine and Atezolizumab for treating chronic myelomonocytic leukemia?

The research does not provide direct evidence of the effectiveness of Guadecitabine and Atezolizumab for chronic myelomonocytic leukemia, but it highlights the need for new treatment approaches due to the poor prognosis and limited effectiveness of current therapies. ^{1 2 3 4 5}

Is the combination of Guadecitabine and Atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been used safely in humans for various cancers, including bladder cancer and breast cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include immune-related issues like rash and thyroid problems. The safety profile of Atezolizumab is generally considered acceptable based on clinical trials. ^{6 7 8 9 10}

What makes the drug combination of Guadecitabine and Atezolizumab unique for treating chronic myelomonocytic leukemia?

The combination of Guadecitabine and Atezolizumab is unique because it combines a hypomethylating agent (Guadecitabine) with an immune checkpoint inhibitor (Atezolizumab), potentially offering a novel approach by targeting both the cancer cells and the immune system, unlike standard treatments that primarily focus on hypomethylating agents alone. ^{3 4 11 12 13}

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of guadecitabine when given together with atezolizumab and to see how well they work in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia that has spread to other places in the body and has come back or does not respond to treatment. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of cancer cells to grow and spread. Giving guadecitabine and atezolizumab may work better in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Research Team

Casey O'Connell, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with advanced Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) that has returned or isn't responding to treatment. Participants must have tried specific drugs before, be able to follow the study plan, and not be pregnant or fathering a child. They should also meet certain health criteria like normal organ function tests.

Inclusion Criteria

Subject has signed and dated informed consent

I agree to not have unprotected sex or donate sperm.

Aspartate aminotransferase (ALT) and alanine aminotransferase (AST) =< 3 x ULN

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I haven't had a serious infection needing strong medicine or a hospital stay in the last 28 days.

I have an autoimmune disease, but it's not vitiligo, type 1 diabetes, or hypothyroidism needing hormone therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive guadecitabine subcutaneously on days 1-5 and atezolizumab intravenously on days 8 and 22. Courses repeat every 28 days for up to 24 months.

Up to 24 months

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 or 90 days and every 6 months thereafter

Treatment Details

Interventions

• Atezolizumab
• Guadecitabine

Trial Overview The trial is testing how well guadecitabine works with atezolizumab in treating MDS/CMML. Guadecitabine may block enzymes needed for cancer cell growth, while atezolizumab, an antibody, might stop cancer cells from growing and spreading.

Participant Groups

Group I: Treatment (guadecitabine, atezolizumab) Experimental Treatment 2 Interventions

Patients receive guadecitabine SC on days 1-5 and atezolizumab IV over 30-60 minutes on days 8 and 22. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Van Andel Research Institute

Collaborator

Trials

28

Recruited

5,200+

Findings from Research

Chronic myelomonocytic leukemia (CMML) has a poor prognosis with a median overall survival of about 2 years and a significant risk of transforming into acute myeloid leukemia (15-20% over 5 years), highlighting the need for better understanding and treatment options.

Current treatment options are limited, with only two FDA-approved drugs (5-azacitidine and decitabine) and allogeneic hematopoietic stem cell transplantation being the only curative approach, which carries high risks of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics. Mangaonkar, AA., Patnaik, MM.[2021]

Chronic myelomonocytic leukemia (CMML) is characterized by specific gene mutations and cytogenetic abnormalities that can help stratify patients into risk groups, guiding treatment decisions; common mutations include TET2, SRSF2, and ASXL1, with ASXL1 mutations linked to worse outcomes.

Allogeneic stem cell transplantation is the preferred treatment for younger patients with poor prognostic factors, while hypomethylating agents may be considered for those ineligible for transplantation, highlighting the need for a consensus on treatment guidelines and response criteria for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic myelomonocytic leukemia prognostic classification and management: evidence base and current practice. Selimoglu-Buet, D., Solary, E.[2021]

Chronic myelomonocytic leukemia (CMML) shows increased sensitivity of myeloid progenitors to granulocyte macrophage-colony stimulating factor, indicating a need for targeted therapies.

Ruxolitinib, a JAK1 and JAK2 inhibitor, has been demonstrated to induce objective responses in patients with CMML, suggesting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia. Solary, E.[2021]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Chronic myelomonocytic leukemia (CMML) has a poor prognosis with a median overall survival of only 2-3 years, and current treatments like hypomethylating agents do not significantly change the disease's natural course.

New therapeutic strategies, including combination therapies with novel agents such as sotatercept and ruxolitinib, are being explored in clinical trials, highlighting the need for innovative approaches to effectively target CMML and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia. Renneville, A., Patnaik, MM., Chan, O., et al.[2023]

References

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

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics. [2021]

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

Proposals for Clinical Trials in Chronic Myelomonocytic Leukemia. [2023]

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

Chronic myelomonocytic leukemia prognostic classification and management: evidence base and current practice. [2021]

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

Unplugging JAK/STAT in Chronic Myelomonocytic Leukemia. [2021]

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

Current Management and Recent Advances in the Treatment of Chronic Myelomonocytic Leukemia. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Successful management of therapy-related chronic myelomonocytic leukemia with cytarabine, aclarubicin, and azacitidine following tegafur/gimeracil/oteracil. [2023]

12. China pubmed.ncbi.nlm.nih.gov

[Clinical Characteristics and Survival Analysis of Patients with Chronic Myelomonocytic Leukemia]. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia. [2023]