Description:
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).
Title
- Brief Title: A Study of JNJ-75276617 in Participants With Acute Leukemia
- Official Title: A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants With Acute Leukemia
Clinical Trial IDs
- ORG STUDY ID:
CR108998
- SECONDARY ID:
2020-005967-30
- SECONDARY ID:
75276617ALE1001
- NCT ID:
NCT04811560
Conditions
- Acute Leukemias
- Acute Myeloid Leukemia
- Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
JNJ-75276617 | | JNJ-75276617 |
Purpose
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).
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
JNJ-75276617 | Experimental | Participants in Part 1 (dose escalation) will receive JNJ-75276617 orally on a 28-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) has been identified. Food effect cohort participants in Part 1 will receive JNJ-75276617 orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition. Participants in Part 2 (dose expansion) will receive JNJ-75276617 orally at one of the RP2D(s) determined in Part 1. | |
Eligibility Criteria
Inclusion Criteria:
- 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 * 10^9/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 (m^2)
- 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
Exclusion Criteria:
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Secondary Outcome Measures
Measure: | Plasma Concentration of JNJ-75276617 |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | Plasma concentration of JNJ-75276617 will be reported. |
Measure: | Number of Participants with Depletion of Leukemic Blasts |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | Number of participants with depletion of leukemic blasts will be reported. |
Measure: | Number of Participants with Differentiation of Leukemic Blasts |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | Number of participants with differentiation of leukemic blasts will be reported. |
Measure: | Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | Changes in expression of menin-KMT2A target genes will be reported. |
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | ORR is defined as the percentage of participants who achieve complete remission (CR), CR with incomplete hematologic recovery (CRi) and CR with partial hematologic recovery (CRh). |
Measure: | Duration of Response (DOR) |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. |
Measure: | Time to Response (TTR) |
Time Frame: | Up to 2 years and 7 months |
Safety Issue: | |
Description: | TTR is defined for the responders as the time from the date of the first dose of JNJ-75276617 to the date of the first documented response. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 11, 2021