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A Study of JNJ-75276617 in Participants With Acute Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04811560
Recruitment Status : Recruiting
First Posted : March 23, 2021
Last Update Posted : May 31, 2023
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Acute Leukemias Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Drug: JNJ-75276617 Phase 1

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 10 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants With Acute Leukemia
Actual Study Start Date : May 19, 2021
Estimated Primary Completion Date : December 26, 2023
Estimated Study Completion Date : June 20, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arms and Interventions
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Arm Intervention/treatment
Experimental: JNJ-75276617
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. Participants in Part 2 (dose expansion) will receive JNJ-75276617 orally at one of the RP2D(s) determined in Part 1. Food effect cohort (optional) participants will receive JNJ-75276617 orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition.
 Drug: JNJ-75276617
JNJ-75276617 is administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years and 10 months ]
    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.

  2. Number of Participants with AEs by Severity [ Time Frame: Up to 2 years and 10 months ]
    Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

  3. Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 28 days Cycle 1 ]
    Percentage of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.


Secondary Outcome Measures :
  1. Plasma Concentration of JNJ-75276617 [ Time Frame: Up to 2 years and 10 months ]
    Plasma concentration of JNJ-75276617 will be reported.

  2. Number of Participants with Depletion of Leukemic Blasts [ Time Frame: Up to 2 years and 10 months ]
    Number of participants with depletion of leukemic blasts will be reported.

  3. Number of Participants with Differentiation of Leukemic Blasts [ Time Frame: Up to 2 years and 10 months ]
    Number of participants with differentiation of leukemic blasts will be reported.

  4. Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes [ Time Frame: Up to 2 years and 10 months ]
    Changes in expression of menin-KMT2A target genes will be reported.

  5. Overall Response Rate (ORR) [ Time Frame: Up to 2 years and 10 months ]
    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).

  6. Duration of Response (DOR) [ Time Frame: Up to 2 years and 10 months ]
    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.

  7. Time to Response (TTR) [ Time Frame: Up to 2 years and 10 months ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (<=) 30 * 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), total serum bilirubin <= 1.5 * ULN (participants with elevated bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated bilirubin is within clinically acceptable range) and renal function; Estimated or measured glomerular filtration rate greater than or equal to (>=) 60 milliliter per minute (mL/min)/1.73 meter square (m^2) per four variable modified diet in renal disease (MDRD) equation
  • 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
  • Active central nervous system (CNS) disease
  • Prior solid organ transplantation
  • QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or for females >= 470 msec. Participants with a family history of Long QT syndrome are excluded
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04811560


Contacts
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Contact: Study Contact 844-434-4210 Participate-In-This-Study@its.jnj.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04811560    
Other Study ID Numbers: CR108998
2020-005967-30 ( EudraCT Number )
75276617ALE1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: March 23, 2021    Key Record Dates
Last Update Posted: May 31, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes