A Study of JNJ-75276617 in Participants With Acute Leukemia
Last Updated   February 26, 2024 - 20:06
OVERVIEW
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Gender
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Age
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Phase
phase 1Researchers test a new drug or treatment in a small group of people for the first time to gather information on its safety, dosing, and side effects. -
Sites
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Status
Recruiting
SUMMARY
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 4 years and 9 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.
CONDITIONS
- Acute Leukemias
- Acute Lymphoblastic Leukemia
- Acute myeloid leukemia
ELIGIBILITY
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), nucleophosmin 1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214) alterations
* Pretreatment clinical laboratory values meeting the following criteria: (a) Hematology: white blood cell (WBC) count less than or equal to (<=) 20 * 10^9/liter (L) (hydroxyurea may be used to lower WBC count at screening and during study; cytoreductive therapy may be considered with sponsor approval; (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 (>=) 50 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 or 1. Adolescent participants only: Performance status >=70 by Lansky scale (for participants less than [<]16 years of age) or >=70 Karnofsky scale (for participants >=16 years of age)
* A participant 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 participant 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, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic 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)
* Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)
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 4 years and 9 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.
LOCATIONS
Country (5) | City or Province (24) | Status |
United States | Boston, MA Dana Farber Cancer Institute |
RECRUITING
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United States | Boston, MA Massachusetts General Hospital |
RECRUITING
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United States | Duarte, CA City of Hope |
RECRUITING
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United States | Houston, TX MD Anderson |
RECRUITING
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United States | Louisville, KY Norton Cancer Institute |
COMPLETED
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United States | Milwaukee, WI Medical College of WI at Froedtert |
RECRUITING
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United States | New York, NY NYU Langone Medical Center |
RECRUITING
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United States | Orange, CA University of California Irvine Medical Center |
COMPLETED
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United States | San Francisco, CA University of California San Francisco |
RECRUITING
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United Kingdom | London Guy's and St Thomas' NHS Foundation Trust |
RECRUITING
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United Kingdom | Manchester The Christie Nhs Foundation Trust |
RECRUITING
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United Kingdom | Oxfordshire, OXF Oxford University Hospitals NHS Trust |
RECRUITING
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Spain | Barcelona, BA Hosp. Clinic de Barcelona |
RECRUITING
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Spain | Barcelona, BA Hosp. Univ. Vall D Hebron |
RECRUITING
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Spain | Madrid, MD Hosp. Univ. Fund. Jimenez Diaz |
RECRUITING
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Spain | Pamplona Clinica Univ. de Navarra |
RECRUITING
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France | Marseille Institut Paoli Calmettes |
RECRUITING
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France | Nantes Cedex 1 CHU de Nantes hotel Dieu |
RECRUITING
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France | Pessac Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie |
RECRUITING
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France | Toulouse Institut Universitaire du Cancer Toulouse Oncopole |
RECRUITING
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France | Tours cedex CHU Bretonneau |
RECRUITING
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Australia | Clayton, VIC Monash Medical Centre |
RECRUITING
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Australia | Perth, WA Royal Perth Hospital |
RECRUITING
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Australia | Southport, QLD Gold Coast University Hospital |
RECRUITING
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