Clinical trial NCT05521087: A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias
Official title: A Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene Alterations
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Acute Leukemias
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Acute Leukemia of Ambiguous Lineage
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-08-30
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2Ds) of JNJ-75276617 in combination with a conventional chemotherapy backbone in pediatric and young adult participants with relapsed/refractory acute leukemia harboring histone-lysine N-methyltransferase 2A1 (\[KMT2A1\], nucleophosmin 1 gene (NPM1), or nucleoporin alterations in Part 1 (Dose Escalation) and to further evaluate safety at the RP2D(s) of JNJ-75276617 in combination with chemotherapy in pediatric and young adult participants with relapsed/refractory acute leukemia harboring KMT2A1, NPM1, or nucleoporin alterations and safety at the RP2D(s) of JNJ-75276617 as monotherapy in a select low burden of disease cohort in Part 2 (Dose Expansion).


Eligibility criteria: Inclusion Criteria:

* Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A) or nucleophosmin 1 gene (NPM1) or nucleoporin (NUP98 or NUP214) alterations
* Performance status greater than or equal to (\>=) 50 by lansky scale (for participants less than \[\<\] 16 years of age) or \>=50 percent (%) karnofsky scale (for participants \>=16 years of age)
* Estimated or measured glomerular filtration rate \>= 60 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2) based on the bed side schwartz formula

Exclusion Criteria:

* Received an allogeneic hematopoietic transplant within 60 days of screening
* Active acute graft-versus-host disease of any grade or chronic graft-versus-host which is not well-controlled
* Received immunosuppressive therapy post hematopoietic transplant within 30 days of enrollment
* Diagnosis of Down syndrome associated leukemia, acute promyelocytic leukemia, juvenile myelomonocytic leukemia
* Diagnosis of fanconi anemia, kostmann syndrome, shwachman diamond syndrome, or any other known bone marrow failure syndrome
* Prior exposure to menin-KMT2A inhibitors
* Prior cancer immunotherapy (ie \[that is\], Chimeric Antigen Receptor-T Cell Therapy \[CAR-T\], inotuzumab, gemtuzumab ozogamicin) 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)

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 3 years 5 months
measure: Number of Participants with AEs by Severity
timeFrame: Up to 3 years 5 months
measure: Number of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: Cycle 1 (28 days)
Secondary outcomes:
measure: Plasma Concentration of JNJ-75276617
timeFrame: Up to 3 years 5 months
measure: Number of Participants with Depletion of Leukemic Blasts
timeFrame: Up to 3 years 5 months
measure: Number of Participants with Differentiation of Leukemic Blasts
timeFrame: Up to 3 years 5 months
measure: Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation
timeFrame: Up to 3 years 5 months
measure: Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)
timeFrame: Up to 3 years 5 months
measure: Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL)
timeFrame: Up to 3 years 5 months
measure: Time to Response (TTR)
timeFrame: Up to 3 years 5 months
measure: Duration of Response (DOR)
timeFrame: Up to 3 years 5 months
measure: Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
timeFrame: Up to 3 years 5 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals - N.C. Childrens Hospital
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Children's Wisconsin - Milwaukee Hospital
state: Wisconsin
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: