Decitabine + Venetoclax for Acute Myeloid Leukemia Maintenance Therapy

Overseen By Benjamin Tomlinson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Benjamin Tomlinson

Must not be taking: HMA/VEN therapy

Disqualifiers: Pregnancy, Active infection, Uncontrolled malignancy, Congestive heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year or until relapse or unacceptable toxicity

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to prevent relapse in individuals with acute myeloid leukemia or myelodysplastic syndromes following a bone marrow transplant. It focuses on using low doses of two drugs, decitabine (a chemotherapy drug) and venetoclax (a targeted therapy), to gently maintain health and control cancer with fewer side effects. Participants will receive these treatments alongside their standard post-transplant care. This trial may suit those who have recently undergone a bone marrow transplant and are within 40 days post-transplant, with no active infections or severe complications. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering a chance to be among the first to receive this new approach.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on other planned post-transplant maintenance therapy, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using decitabine and venetoclax together is generally safe and well-tolerated for people with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In earlier studies, many patients responded well to these drugs. Specifically, about 60-70% of older AML patients experienced complete remission, meaning their cancer greatly decreased.

While these treatments appear promising, some side effects were reported. Common issues included low blood cell counts and infections, typical for many cancer treatments. However, proper medical care managed these side effects effectively.

In summary, decitabine and venetoclax have proven effective and tolerable, with side effects similar to other cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Decitabine and Venetoclax for maintaining remission in acute myeloid leukemia (AML) because these drugs offer a unique approach to post-transplant care. Unlike traditional treatments that may not effectively target residual leukemia cells after a stem cell transplant, Venetoclax is a BCL-2 inhibitor that helps to induce cancer cell death by disrupting their survival signals. Decitabine, on the other hand, is a hypomethylating agent that reactivates cancer-suppressing genes. Together, they provide a targeted maintenance therapy that could potentially keep leukemia at bay longer with a lower risk of relapse.

What evidence suggests that decitabine and venetoclax might be an effective treatment for acute myeloid leukemia?

Research shows that combining decitabine and venetoclax may help treat acute myeloid leukemia (AML). In one study, this combination helped 60-70% of older AML patients achieve complete remission, meaning their cancer was completely reduced. Another study found that 62% of patients had a positive response, indicating their cancer reacted well to the treatment. This trial will evaluate the combination of decitabine and venetoclax as a low-dose maintenance chemotherapy for AML post-transplant. This combination has also shown good results for people with high-risk myelodysplastic syndromes, disorders caused by poorly formed or dysfunctional blood cells. Overall, these findings suggest the treatment could effectively manage AML and possibly other related conditions. ^{2 5 6 7 8}

Who Is on the Research Team?

Benjamin Tomlinson, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

James Ignatz-Hoover, MD, PhD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Claudio Brunstein, MD, PhD

Principal Investigator

Cleveland Clinic Foundation, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute myeloid leukemia or related conditions, who've had a bone marrow transplant. They should be at high risk of cancer returning but currently without severe infection or organ rejection (GVHD grade II+). Participants need proper liver and kidney function, good physical health (ECOG 0-1), and must not be pregnant or breastfeeding.

Inclusion Criteria

You can understand and sign a paper that explains the study and your decision to take part in it.

Your total bilirubin level is less than 2.0 mg/dL, unless you have a known condition called Gilbert's syndrome.

Your kidneys work well enough to filter out waste products from your blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose decitabine once weekly followed by venetoclax orally approximately 6 hours afterwards as maintenance therapy post-transplant

1 year or until relapse or unacceptable toxicity

Weekly visits for decitabine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Venetoclax

Trial Overview The study tests if low-dose chemotherapy with decitabine and venetoclax can prevent cancer from coming back after a bone marrow transplant. Patients will get standard care plus weekly decitabine followed by venetoclax pills, continuing up to one year unless the disease returns or they experience significant side effects.

How Is the Trial Designed?

Group I: Low dose maintenance chemotherapy Experimental Treatment 2 Interventions

Participants will receive low dose chemotherapy as a maintenance therapy post-transplant. Participants must enroll by post-transplant day 40. Treatment will consist of once weekly 5 mg/m2 decitabine followed by 400 mg venetoclax orally approximately 6 hours afterwards. Participants will continue maintenance therapy for one year or unacceptable toxicity. Participants will otherwise receive post Allogeneic hematopoietic stem cell transplant (alloSCT) care and disease monitoring as per institutional standards.

Who Is Running the Clinical Trial?

Benjamin Tomlinson

Lead Sponsor

Trials

4

Recruited

110+

Published Research Related to This Trial

In a phase 2 trial involving 168 patients with acute myeloid leukaemia (AML), the combination of venetoclax and a 10-day regimen of decitabine resulted in a high overall response rate of 74%, with particularly impressive results in newly diagnosed AML patients (89%).

The treatment demonstrated a manageable safety profile, with common adverse events including neutropenia and infections, and a 30-day mortality rate of only 3.6%, indicating that this combination therapy is both effective and relatively safe for older patients or those unfit for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. DiNardo, CD., Maiti, A., Rausch, CR., et al.[2021]

In a study involving 145 older patients (median age 74) with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, the combination of venetoclax with decitabine or azacitidine resulted in a high complete remission (CR) rate of 67%, demonstrating its efficacy in this challenging population.

The treatment was well tolerated, with no cases of tumor lysis syndrome reported, and the median overall survival was 17.5 months, indicating that venetoclax combined with hypomethylating agents is a promising option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. DiNardo, CD., Pratz, K., Pullarkat, V., et al.[2021]

A once-weekly low-dose decitabine (LDDec) combined with venetoclax (VEN) showed high efficacy in treating elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving an overall response rate of 88% for AML and 64% for MDS in a retrospective study of 39 patients.

Patients receiving the LDDec/VEN regimen experienced longer treatment durations and a trend towards higher transfusion independence compared to those on standard dosing, suggesting that this approach may reduce severe myelosuppression while maintaining effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. Levitz, D., Saunthararajah, Y., Fedorov, K., et al.[2023]

Venetoclax, a BCL-2 inhibitor, shows promise in combination therapies for newly diagnosed or relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving high remission rates and deep molecular responses.

Despite these encouraging results, there are concerns about side effects such as incomplete blood count recovery and increased infection rates, particularly when used with chemotherapy, and more research is needed to understand the long-term effectiveness and durability of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. Shimony, S., Stone, RM., Stahl, M.[2023]

In a study of 22 heavily pre-treated patients with relapsed or refractory acute myeloid leukaemia (RR-AML), the combination of venetoclax and decitabine resulted in a 45.5% overall response rate, with 40.9% achieving complete remission, demonstrating its efficacy in a real-world setting.

While the treatment was effective, it was associated with significant side effects, including grade IV neutropenia and thrombocytopenia in all patients, but no deaths were attributed to the treatment side effects, indicating that the adverse effects were manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. Tong, J., Zhao, N., Hu, X., et al.[2022]

In a study of 6 children with refractory or relapsed acute myeloid leukemia (AML), the combination of venetoclax, azacitidine, and cladribine (VAC regimen) resulted in significant treatment responses, with 4 achieving complete remission and 1 showing partial remission.

Despite severe side effects like grade IV neutropenia and thrombocytopenia, there were no treatment-related deaths or infections, indicating that the VAC regimen is both effective and safe for this vulnerable patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. DU, WW., Liu, SX., Wang, Y., et al.[2023]

In a study of 81 patients with acute myeloid leukemia (AML) receiving venetoclax with decitabine or azacitidine, 72.8% experienced infections, with the most common pathogens being Candida albicans and Klebsiella pneumonia.

The study found that the incidence of infectious complications was lower with this treatment compared to conventional chemotherapy, and high leukemia burden and fever were identified as significant risk factors for developing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. Zhu, LX., Chen, RR., Wang, LL., et al.[2022]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7549397/

Ten-day Decitabine with Venetoclax in Acute Myeloid Leukemia DEC10-VEN was moderately effective in the R/R cohort with ORR of 62%, median DOR of 16·8 months, and 1-year OS of 62% in R/R de novo AML. These outcomes compare ...

2. venclextahcp.com venclextahcp.com/aml/efficacy/ven-aza/survival-results.html

VEN+AZA: Overall survival (OS) data from the VIALE-A trial Fatal adverse reactions occurred in 23% of patients who received VENCLEXTA in combination with azacitidine, with the most frequent (≥2%) being pneumonia (4%), ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6318429/

Venetoclax with decitabine/azacitidine for AML in elderly Venetoclax plus decitabine or azacitidine showed tolerable safety and favorable overall response rate (CR + CRi rate: 67%) in elderly patients with AML. This ...

4. healthtree.org healthtree.org/aml/community/articles/venetoclax-decitabine-help-senior-aml-transplant

Venetoclax & Decitabine Help AML Transplant Chance Venetoclax combined with decitabine has been effective in helping 60-70% of senior AML patients achieve complete remission, meaning a full reduction in cancer ...

5. onclive.com onclive.com/view/venetoclax-plus-10-day-decitabine-produces-responses-in-high-risk-mds-aml

Venetoclax Plus Decitabine for High-Risk MDS, AML Responses Venetoclax and decitabine combination shows high overall response rates in AML and high-risk MDS, with CR/CRi rates varying by patient group.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11707511/

Venetoclax-Based Combination Regimens in Acute Myeloid ... In this study, we provide an overview of the incorporation of venetoclax into AML treatment and a discussion of practical considerations and areas of unmet ...

7. venclextahcp.com venclextahcp.com/aml/efficacy/ven-dec/study-design.html

M14-358 Clinical Trial Study Design - venclexta Learn more about how the efficacy and safety of VENCLEXTA® + decitabine in AML were studied in the M14-358 clinical trial. See full safety and Prescribing ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03941964

NCT03941964 | A Study of the Effectiveness of Venetoclax ... A study evaluating the effectiveness and safety of venetoclax, in combination with azacitidine or decitabine, in an outpatient setting for treatment-naïve ...