Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Orange, California and other locations
Dates
study started
estimated completion

Description

Summary

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of JNJ-75276617 in Part 1 (Dose Escalation) and to determine safety and tolerability at the RP2D(s) in Part 2 (Dose Expansion).

Official Title

A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants With Acute Leukemia

Details

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells (myeloid blasts) in the peripheral blood, bone marrow, and other tissues. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy propagated by impaired differentiation, proliferation, and accumulation of lymphoid progenitor cells in the bone marrow and/or extramedullary sites. JNJ-75276617 is an orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between histone-lysine N-methyltransferase 2A ([KMT2A], also called mixed-lineage leukemia 1 [MLL1]; wild-type and fusion) and menin, with activity in leukemic cell lines and primary leukemia patient or patient-derived samples with either KMT2A alterations including gene rearrangements (KMT2A-r), duplications, and amplification, or nucleophosmin 1 gene (NPM1) alterations. The primary goal of this FIH study is to establish the recommended Phase 2 dose (RP2D) of JNJ-75276617 with an acceptable safety profile. The total duration of the study is up to 2 years and 7 months. Safety assessment will include adverse events (AEs), serious adverse events (SAEs), physical examination, Eastern Cooperative Oncology Group (ECOG) performance status, vital signs, electrocardiogram, clinical safety laboratory assessment and pregnancy testing.

Keywords

Acute Leukemias Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Acute Disease JNJ-75276617

Eligibility

You can join if…

Open to people ages 18 years and up

  • Relapsed or refractory acute leukemia and has exhausted, or is ineligible for, available therapeutic options
  • Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A) or nucleophosmin 1 gene (NPM1) alterations
  • Pretreatment clinical laboratory values meeting the following criteria: (a)

Hematology: white blood cell (WBC) count less than or equal to (<=) 50 * 109/liter (L) (hydroxyurea may be used to lower WBC count at screening and during study; (b)

Chemistry: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 * upper limit of normal (ULN), Corrected serum bilirubin <= 1.5 * ULN (participants with elevated bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated bilirubin is within normal range) and renal function; Estimated or measured glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute (mL/min)/1.73 meter square (m2)

  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
  • 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
  • A male must agree to all the following during the study and for 90 days after the last dose of study treatment: A male must agree to all the following during the study and for 90 days after the last dose of study treatment: (a) wear a condom when engaging in any activity that allows for passage of ejaculate to another person; (b) not to donate sperm or freeze for future use for the purpose of reproduction. In addition, the participant should be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak

You CAN'T join if...

  • Acute promyelocytic leukemia according to World Health Organization (WHO) 2016 criteria
  • Known central nervous system (CNS) involvement
  • Prior solid organ transplantation
  • QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or for females >= 470 msec
  • Exclusion criteria related to stem cell transplant: a. Willing and able to undergo allogeneic stem cell transplant (if clinically indicated); b. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; c. Has evidence of graft versus host disease; d. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; e. Requires immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement)
  • Chemotherapy, targeted therapy, immunotherapy, or radiotherapy within 4 weeks or 5 half-lives (whichever is shorter) before the planned first dose of study treatment

Locations

  • University of California Irvine Medical Center not yet accepting patients
    Orange California 92868 United States
  • City of Hope accepting new patients
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Janssen Research & Development, LLC
Links
To learn how to participate in this trial please click here.
ID
NCT04811560
Phase
Phase 1
Study Type
Interventional
Last Updated