96 Participants Needed

Ivosidenib + Venetoclax +/- Azacitidine for Leukemia

Recruiting at 4 trial locations
CD
Courtney DiNardo, MD profile photo
Overseen ByCourtney DiNardo, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but you cannot use other chemotherapeutic or anti-leukemic agents during the study, except for certain exceptions like intrathecal chemotherapy or hydroxyurea. Also, you should not take strong CYP3A inducers within 3 days of starting the study therapy.

What data supports the effectiveness of the drug combination Ivosidenib, Venetoclax, and Azacitidine for treating leukemia?

Venetoclax combined with azacitidine is used as a first-line therapy for elderly patients with acute myeloid leukemia (AML), achieving a complete remission rate of 70% or more. Additionally, venetoclax has shown high response rates in chronic lymphocytic leukemia (CLL), indicating its potential effectiveness in blood cancers.12345

Is the combination of Ivosidenib, Venetoclax, and Azacitidine safe for humans?

Venetoclax, when used with azacitidine, has shown an acceptable safety profile in patients with acute myeloid leukemia and chronic lymphocytic leukemia, with manageable side effects like neutropenia (low white blood cell count). Common side effects include blood-related and digestive issues, but these are generally manageable with supportive care and dose adjustments.12367

What makes the drug combination of Ivosidenib, Venetoclax, and Azacitidine unique for treating leukemia?

This drug combination is unique because it includes Ivosidenib, which targets a specific genetic mutation (IDH1) in leukemia cells, alongside Venetoclax and Azacitidine, which are already used together for older patients with acute myeloid leukemia who cannot undergo standard chemotherapy. This combination may offer a new option for patients with specific genetic profiles.12458

What is the purpose of this trial?

This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutated hematologic malignancies. Venetoclax and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ivosidenib and venetoclax with azacitidine may work better in treating patients with hematologic malignancies compared to ivosidenib and venetoclax alone.

Research Team

Courtney D. DiNardo | MD Anderson ...

Courtney DiNardo, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with IDH1-mutated blood cancers like AML, MDS, or MPN who are either treatment-naive and ineligible for standard chemotherapy or have relapsed/refractory disease. Participants must be in stable condition with acceptable organ function and agree to contraception. Those previously treated with ivosidenib/venetoclax, active infections (HBV/HCV/HIV), uncontrolled medical conditions, severe allergies to study drugs, or on certain medications are excluded.

Inclusion Criteria

I have AML or a related condition and cannot have standard chemotherapy.
My liver is functioning well, according to my recent tests.
I haven't had cancer treatment in the last 7 days.
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Exclusion Criteria

I am not pregnant, using effective birth control, or not of childbearing potential.
My white blood cell count is above 25 x 10⁹/L.
Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax orally daily on days 1-14, ivosidenib orally daily on days 15-28 of cycle 1 and days 1-28 of subsequent cycles, and may receive azacitidine intravenously or subcutaneously on days 1-7. Cycles repeat every 28 days.

28 days per cycle, up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then monthly for 3 years.

3 years

Treatment Details

Interventions

  • Azacitidine
  • Ivosidenib
  • Venetoclax
Trial Overview The trial examines the effectiveness of combining venetoclax and ivosidenib with or without azacitidine in treating hematologic malignancies. It aims to determine the best dose while assessing side effects when these drugs work together compared to using just venetoclax and ivosidenib.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (venetoclax, ivosidenib, azacitidine)Experimental Treatment3 Interventions
Patients receive venetoclax PO daily on days 1-14. Patients also receive ivosidenib PO daily on days 15-28 of cycle 1 and days 1-28 of subsequent cycles. Patients may also receive azacitidine IV over 30-60 minutes or SC on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

🇺🇸
Approved in United States as Tibsovo for:
  • Acute myeloid leukemia (AML) with IDH1 mutation
🇪🇺
Approved in European Union as Tibsovo for:
  • Acute myeloid leukemia (AML) with IDH1 mutation

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.
While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia .Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]
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.
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]
In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.
Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia.Blair, HA.[2021]

References

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. [2022]
SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. [2023]
[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. [2023]
Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. [2023]
Administration of combined venetoclax and azacitidine in a patient with acute myeloid leukemia and multiple comorbidities undergoing dialysis: A case report. [2023]
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