6 Participants Needed

Navitoclax + Venetoclax + Decitabine for Myelodysplastic Syndrome

NP
GK
Overseen ByGina Keiffer, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Thomas Jefferson University
Must be taking: Hypomethylating agents
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This phase Ib/II trial tests the safety, side effects, and best dose of navitoclax in combination with venetoclax and decitabine in treating patients with higher risk myelodysplastic syndrome (MDS) that has come back after initial treatment or was not responsive to initial treatment. This study will also look at the effectiveness of the treatment combination and patient's quality of life while on these medications. Navitoclax is an oral drug that works as an inhibitor of the BCL-2 family of proteins, which are often overly expressed in a wide variety of cancers and are linked to tumor drug resistance. This drug blocks some of the enzymes that keep cancer cells from dying. Venetoclax is an oral drug that works as an inhibitor of BCL-2 proteins that works very similarly to navitoclax by blocking the action of a certain proteins in the body that helps cancer cells survive which helps to kill cancer cells. Decitabine is an intravenous drug. It is a hypomethylating agent which means it interferes with deoxyribonucleic acid (DNA) methylation. DNA methylation is a major factor that regulates gene expression in cells, and an increase in DNA methylation can block the genes that regulate cell division and growth. When these genes are blocked the overall result allows or promotes cancer as there is no control over cell growth. Decitabine stops cells from making DNA and may kill cancer cells. Participation in this trial may improve the understanding of both chemotherapy response in MDS and mechanisms of resistance to current therapies.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that interfere with blood clotting or platelet function, except for low-dose aspirin and certain blood thinners, which must be stopped at least 3 days before starting the trial. If you are on these medications and cannot stop, you will not be able to participate.

What data supports the effectiveness of the drug combination of Navitoclax, Venetoclax, and Decitabine for Myelodysplastic Syndrome?

Research shows that Venetoclax combined with Decitabine has been effective in treating acute myeloid leukemia (AML), especially in older patients or those who cannot undergo intensive chemotherapy. This combination has shown promising results in achieving remission and improving survival rates, suggesting potential benefits for similar blood disorders like Myelodysplastic Syndrome.12345

Is the combination of Navitoclax, Venetoclax, and Decitabine safe for humans?

The combination of Venetoclax and Decitabine has been studied for safety in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It is generally considered safe, but it can cause side effects like myelosuppression (a decrease in blood cell production), which may be severe, especially in elderly or frail patients.12456

What makes the drug combination of Navitoclax, Venetoclax, and Decitabine unique for treating myelodysplastic syndrome?

This drug combination is unique because it combines Navitoclax, a BCL-2 family protein inhibitor, with Venetoclax, another BCL-2 inhibitor, and Decitabine, a hypomethylating agent, which may enhance the treatment's effectiveness by targeting cancer cells in different ways. This approach is novel compared to standard treatments that typically use only one or two of these components.14578

Eligibility Criteria

Adults with aggressive myelodysplastic syndrome (MDS) who have tried azacitidine or decitabine and venetoclax without success. They must be able to swallow pills, not pregnant or breastfeeding, willing to use contraception, and have an ECOG Performance Status of 0-2 indicating they are relatively active.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.
Creatinine clearance >= 40 mL/min, calculated with the use of the 24-hour creatinine clearance or modified Cockcroft-Gault equation
Provide signed and dated informed consent form
See 21 more

Exclusion Criteria

Known allergic reactions to components of the study product(s)
Pregnancy or lactation or intending to become pregnant during the study
I do not have uncontrolled HIV, HBV, or HCV with a detectable viral load.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Cycle 1

Participants receive navitoclax, venetoclax, and decitabine with bone marrow biopsy and blood sample collection

4 weeks
Multiple visits for drug administration and sample collection

Treatment Cycle 2 and Beyond

Participants continue receiving navitoclax, venetoclax, and decitabine with bone marrow biopsy and blood sample collection

28 days per cycle, up to 6 cycles
Multiple visits for drug administration and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
Every 3 months

Survival Follow-up

Participants are followed for overall survival

2 years from enrollment of the last patient

Treatment Details

Interventions

  • Decitabine
  • Navitoclax
  • Venetoclax
Trial OverviewThe trial is testing the safety and optimal dose of navitoclax in combination with venetoclax and decitabine for MDS patients whose disease returned or didn't respond to initial treatment. It aims to assess how effective this drug combo is on patient health outcomes including quality of life.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (navitoclax, decitabine, venetoclax)Experimental Treatment7 Interventions

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

🇪🇺
Approved in European Union as Dacogen for:
  • Acute myeloid leukemia
  • Myelodysplastic syndromes
🇺🇸
Approved in United States as Dacogen for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia
🇨🇦
Approved in Canada as Dacogen for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia
🇯🇵
Approved in Japan as Dacogen for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials
475
Recruited
189,000+

AbbVie

Industry Sponsor

Trials
1,079
Recruited
535,000+
Founded
2013
Headquarters
North Chicago, USA
Known For
Immunology treatments
Top Products
Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael profile image

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

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.
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]
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.
A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML.Levitz, D., Saunthararajah, Y., Fedorov, K., et al.[2023]
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.
Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia.DiNardo, CD., Pratz, K., Pullarkat, V., et al.[2021]

References

10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. [2021]
A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. [2023]
Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. [2021]
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]
Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. [2022]
Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. [2022]
Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. [2023]
Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]