JNJ-75276617 Combination Therapy for Acute Myeloid Leukemia

Recruiting at 44 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Acute promyelocytic leukemia, Down syndrome, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug JNJ-75276617 Combination Therapy for Acute Myeloid Leukemia?

The research highlights the effectiveness of similar treatments, such as the combination of venetoclax with other drugs, which has shown promising results in treating acute myeloid leukemia (AML). Additionally, investigational menin inhibitors and other novel drug combinations have demonstrated encouraging response rates in AML patients, suggesting potential for new therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests JNJ-75276617, an oral drug that blocks a key protein interaction in leukemia cells. It targets adults with AML who have specific genetic changes making their disease hard to treat. The drug aims to stop cancer cells from growing and spreading.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with Acute Myeloid Leukemia (AML) as per WHO criteria, including those with de novo or secondary AML and relapsed/refractory cases. Participants must be in relatively good health (ECOG grade 0-2), have adequate organ function, not require supplemental oxygen, and women of childbearing potential must test negative for pregnancy.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

Willing and able to adhere to the prohibitions and restrictions specified in this protocol

A woman of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment

Exclusion Criteria

I have received a solid organ transplant.

I need extra oxygen to help me breathe properly.

I have been diagnosed with a specific type of leukemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection

Participants receive bleximenib in combination with AML-directed therapies to determine the recommended Phase 2 dose (RP2D)

Up to 3 years 3 months

Dose Expansion

Participants receive bleximenib in combination with AML-directed therapies at the RP2D to evaluate safety and tolerability

Up to 3 years 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-75276617

Trial Overview The study tests JNJ-75276617 combined with other AML therapies like Venetoclax, Azacitidine, Cytarabine, Daunorubicin or Idarubicin to find the safest and most effective dose. It aims to establish a recommended Phase 2 dose and assess safety at that level.

Participant Groups

Group I: Arm C: Newly Diagnosed Chemotherapy Eligible Setting Experimental Treatment 3 Interventions

Participants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants \>= 18 to \<75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy.

Group II: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting Experimental Treatment 3 Interventions

Participants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are \>=75 years of age or \>=18 years of age to \<75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.

Group III: Arm A: Relapsed/Refractory Setting Experimental Treatment 3 Interventions

Participants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (\>=) 12 years and less than (\<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s).

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

In 2017, the FDA approved five new drugs for treating acute myeloid leukemia (AML), including targeted therapies for specific genetic mutations (FLT3 and IDH2) and a new formulation of cytarabine-daunorubicin for certain types of AML.

The combination of the BCL-2 inhibitor venetoclax with low-intensity therapy showed promising results for older patients who are not suitable for intensive chemotherapy, indicating a shift towards more tailored treatment options in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Wei, AH., Tiong, IS.[2022]

Recent advancements in the treatment of acute myeloid leukemia (AML) include new targeted therapies like CPX-351 and gemtuzumab ozogamicin, which have improved outcomes for specific patient subgroups.

The combination of midostaurin with intensive chemotherapy for FLT3-mutated AML and the use of IDH inhibitors (enasidenib and ivosidenib) have shown significant efficacy, particularly in relapsed cases, highlighting the potential of targeted therapies in AML management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Treatment Options for Acute Myeloid Leukemia in 2019. Cerrano, M., Itzykson, R.[2020]

The combination of vosaroxin and venetoclax synergistically induces apoptosis in acute myeloid leukemia (AML) cell lines and primary patient samples, suggesting a potent anti-leukemic effect.

This combination treatment effectively targets AML progenitor cells while sparing normal hematopoietic progenitor cells, indicating a potentially safer therapeutic option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. Liu, F., Knight, T., Su, Y., et al.[2020]

A patient with FLT3 positive acute myeloid leukemia achieved complete clinical and molecular remission after adding sorafenib to their chemotherapy regimen, indicating its efficacy in this context.

The combination treatment was well-tolerated, with only mild side effects reported, suggesting that sorafenib can be safely integrated into standard chemotherapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sorafenib in combination with chemotherapy in the induction therapy for FLT3-ITD positive acute monocytic leukemia: a case report and literature review]. Wei, SN., Wei, H., Mi, YC., et al.[2018]

Two investigational menin inhibitors, SNDX-5613 and KO-539, showed promising efficacy in treating relapsed and refractory acute myeloid leukemia (AML), with overall response rates of 53% and 40%, respectively, in patients with specific genetic mutations.

The combination of pivekimab sunirine with azacitidine and venetoclax achieved a 45% overall response rate in relapsed and refractory AML, which increased to 53% in patients who had not previously received venetoclax, highlighting the potential of novel treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents and regimens in acute myeloid leukemia: latest updates from 2022 ASH Annual Meeting. DiNardo, KW., LeBlanc, TW., Chen, H.[2023]

References

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

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. [2022]

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

New Treatment Options for Acute Myeloid Leukemia in 2019. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. [2020]

4. China pubmed.ncbi.nlm.nih.gov

[Sorafenib in combination with chemotherapy in the induction therapy for FLT3-ITD positive acute monocytic leukemia: a case report and literature review]. [2018]

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

Novel agents and regimens in acute myeloid leukemia: latest updates from 2022 ASH Annual Meeting. [2023]