JNJ-64264681 for Non-Hodgkin's Lymphoma and Leukemia

Recruiting at 15 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Disqualifiers: CNS involvement, Organ transplant, Allergies, others

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

Compensation: Varies

Number of Visits: Unknown

85 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called JNJ-64264681 to find the best dose and ensure it is safe. It focuses on patients with specific blood cancers, namely B cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. The drug aims to attack and kill the cancer cells in these patients.

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 an investigational drug, you must stop it at least two weeks before starting the study drug.

What safety information is available for JAK inhibitors like JNJ-64264681?

JAK inhibitors, similar to JNJ-64264681, have been linked to infections (like herpes and flu), muscle and joint issues, blood clots, and skin cancers. These findings are based on data from other JAK inhibitors, such as ruxolitinib, tofacitinib, and baricitinib, used for different conditions. ^{1 2 3 4 5}

What makes the drug JNJ-64264681 unique for treating Non-Hodgkin's Lymphoma and Leukemia?

JNJ-64264681 is unique because it is an irreversible covalent inhibitor of Bruton's tyrosine kinase, which means it forms a permanent bond with the enzyme, potentially leading to more sustained inhibition compared to reversible inhibitors. This mechanism of action is different from other treatments that may target different pathways or use reversible inhibition. ^{6 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with certain types of blood cancers, like Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia. They should be relatively healthy (ECOG grade 0 or 1), able to follow the study rules, and have normal heart rhythm readings. Women must test negative for pregnancy and agree not to donate eggs during the study.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Participants must have cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds based on the average of triplicate assessments performed as close as possible in succession (the full set of triplicates should be completed in less than 10 minutes)

Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 30 days after the last study drug administration

Exclusion Criteria

I haven't taken any experimental drugs or vaccines within the last 2 weeks or five half-lives before starting the study drug.

Participant has received prior solid organ transplantation

My cancer has spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive oral administration of JNJ-64264681 capsule at a dose assigned by the sponsor Study Evaluation Team (SET) in Part 1; and recommended Phase 2 dose (RP2D) determined in Part 1 in cohort expansion treatment group (Part 2).

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-64264681

Trial Overview The trial is testing JNJ-64264681's safety and optimal dose in two parts: first finding the best dose, then checking its safety at that dose in patients with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Participant Groups

Group I: JNJ-64264681: Dose Escalation and Expansion Experimental Treatment 1 Intervention

Participants will receive oral administration of JNJ-64264681 capsule at a dose assigned by the sponsor Study Evaluation Team (SET), based on the available safety, pharmacokinetics, and pharmacodynamics data in dose escalation treatment group (Part 1); and recommended Phase 2 dose (RP2D) determined in Part 1 in cohort expansion treatment group (Part 2).

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

A study analyzing 126,815 safety reports found that the JAK inhibitors ruxolitinib, tofacitinib, and baricitinib are associated with increased risks of infectious adverse events, particularly viral, fungal, and mycobacterial infections.

Tofacitinib specifically showed a significant association with gastrointestinal perforation events, while no significant increase in major cardiovascular events was observed, indicating a need for careful monitoring of these risks in patients using JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Hoisnard, L., Lebrun-Vignes, B., Maury, S., et al.[2023]

In a study of 10 patients with juvenile dermatomyositis (JDM) treated with Janus kinase inhibitors (JAKis) for at least 6 months, 5 patients achieved clinically inactive disease, indicating that JAKis can be effective for refractory cases.

While JAKis showed promise in improving muscle vasculopathy and reducing steroid use, there was a notable risk of herpes zoster infections in some patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. Le Voyer, T., Gitiaux, C., Authier, FJ., et al.[2021]

In a phase III study involving 507 patients with rheumatoid arthritis, peficitinib (100 mg and 150 mg once daily) significantly improved symptoms compared to placebo, with ACR20 response rates of 57.7% and 74.5% respectively at week 12.

Peficitinib was well tolerated overall, although there was a higher incidence of serious infections and herpes zoster compared to placebo, indicating a need for monitoring but no clear dose-dependent increase in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3). Tanaka, Y., Takeuchi, T., Tanaka, S., et al.[2020]

JAK inhibitors, particularly ruxolitinib, have become essential in treating classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) like primary myelofibrosis (PMF) and polycythemia vera (PV), showing significant efficacy over the past several years.

Newer JAK inhibitors, such as pacritinib and Itacitinib, are being explored for their potential benefits, including reduced side effects and improved treatment outcomes, particularly in managing anemia associated with myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium. Griesshammer, M., Sadjadian, P.[2021]

In a phase 2 study involving 104 patients with relapsed or refractory peripheral T-cell lymphoma, golidocitinib demonstrated an objective response rate of 44.3%, indicating significant anti-tumor activity, with 24% of patients achieving a complete response.

While 59% of patients experienced grade 3-4 drug-related adverse events, these were manageable and reversible, suggesting that golidocitinib has a favorable safety profile for further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. Song, Y., Malpica, L., Cai, Q., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. [2023]

2. England pubmed.ncbi.nlm.nih.gov

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. [2021]

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

The promise of Janus kinase inhibitors in the treatment of hematological malignancies. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3). [2020]

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

The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium. [2021]

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

A Phase 1 First-in-Human Pharmacokinetic and Pharmacodynamic Study of JNJ-64264681, a Covalent Inhibitor of Bruton's Tyrosine Kinase. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma. [2019]

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

Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. [2016]