Enasidenib for Chronic Myelomonocytic Leukemia

Overseen By Veronica de Santiago

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stanford University

Must not be taking: Erythropoietic agents

Disqualifiers: Cardiac disease, IDH2 mutations, infections, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing enasidenib to see if it can help patients with certain blood disorders make more red blood cells and need fewer transfusions. The medication works by boosting the body's natural ability to produce red blood cells. Enasidenib is approved by the US FDA for adults with specific types of blood cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain erythropoietic agents (medications that help produce red blood cells) or G-CSF within 30 days of joining the study. It's best to discuss your specific medications with the study team.

How is the drug Enasidenib unique in treating chronic myelomonocytic leukemia?

Enasidenib is unique because it is an oral drug that specifically targets and inhibits mutant IDH2 proteins, which are involved in certain blood cancers. This mechanism helps normalize harmful substances in the body and promotes the maturation of cancerous cells into normal cells, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Tian Yi Zhang, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults with lower risk myelodysplastic syndrome (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML), without IDH2 mutation, who have anemia symptoms like fatigue and shortness of breath. Participants must not have had certain therapies recently, be able to take oral meds, and use effective contraception if applicable. They can't join if they have other causes of anemia, significant heart disease, less than 3 months life expectancy, active infections including HIV or hepatitis B/C.

Inclusion Criteria

No disease-modifying therapy (HMA, hydrea) within 2 months of starting study

ECOG ≤ 3

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

You have anemia caused by factors like low levels of iron, vitamin B12, or folate, or nutritional issues related to certain surgeries, eating disorders, or excessive zinc intake. If these nutritional deficiencies can be fixed, you can be re-evaluated and potentially enrolled in the study if you are no longer deficient and still meet the other requirements.

You have used other medications that help produce red blood cells or boost the immune system within the past month.

Harbor IDH2 somatic mutations by NGS or PCR

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants self-administer enasidenib orally every day to assess safety and efficacy in improving anemia and decreasing transfusion needs

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enasidenib

Trial Overview The study tests whether enasidenib mesylate can safely improve anemia and reduce the need for blood transfusions in MDS/CMML patients without the IDH2 mutation. It's a phase 1b/2 trial where everyone gets increasing doses of enasidenib to see how well it works and what effects it has on their body.

How Is the Trial Designed?

Group I: Enasidenib mesylat Experimental Treatment 1 Intervention

Participants will self administer the enasidenib orally everyday.

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

Approved in United States as Idhifa for:

• Relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation

Approved in European Union as Idhifa for:

• Acute myeloid leukaemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Tian Yi Zhang

Lead Sponsor

Trials

1

Recruited

20+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Published Research Related to This Trial

Enasidenib (Idhifa®) is an oral medication that specifically inhibits the IDH2 enzyme and has been approved in the USA for treating adults with relapsed or refractory acute myeloid leukaemia (AML) with an IDH2 mutation.

The approval of enasidenib marks a significant milestone as it is the first global treatment option specifically targeting IDH2 mutations in AML, highlighting its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib: First Global Approval. Kim, ES.[2022]

Enasidenib is a targeted treatment for relapsed or refractory acute myeloid leukemia that effectively inhibits mutant IDH2 proteins, as shown in a Phase I/II study assessing its safety and efficacy in patients with IDH2 mutations.

The study revealed that enasidenib significantly induces CYP3A enzyme activity, which is important to consider when prescribing other medications that are metabolized by this pathway, due to the potential for drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment. Li, Y., Connarn, JN., Chen, J., et al.[2022]

In a clinical trial involving 107 patients with newly diagnosed mutant-IDH2 acute myeloid leukaemia, the combination of enasidenib and azacitidine significantly improved overall response rates, with 74% of patients responding compared to 36% in the azacitidine-only group.

The combination treatment was well tolerated, with no treatment-related deaths reported, although some patients experienced common grade 3 or 4 adverse events like thrombocytopenia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. DiNardo, CD., Schuh, AC., Stein, EM., et al.[2022]

Enasidenib is an effective oral treatment for relapsed/refractory acute myeloid leukemia (AML) with IDH2 mutations, showing durable complete remissions in about 20% of patients and leading to improved survival in preclinical models.

The drug works by normalizing levels of the oncometabolite (R)-2-hydroxyglutarate, promoting differentiation of leukemic cells, and is generally well tolerated, although it can cause differentiation syndrome as a notable side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib. Krämer, A., Bochtler, T.[2019]

Enasidenib is an effective oral treatment for acute myeloid leukemia (AML) that specifically targets IDH2 mutations, showing clinical improvement in 19.6% of patients and laboratory improvement in 38.8% of cases based on clinical trials.

While enasidenib is generally well-tolerated, it can cause differentiation syndrome, a serious side effect that requires careful monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of enasidenib for the treatment of acute myeloid leukemia. Del Principe, MI., Paterno, G., Palmieri, R., et al.[2019]

Citations

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

Enasidenib: First Global Approval. [2022]

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

Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Enasidenib. [2019]

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of enasidenib for the treatment of acute myeloid leukemia. [2019]