A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias
- Conditions
- Acute LeukemiasAcute Leukemia of Ambiguous LineageAcute Myeloid LeukemiaAcute Lymphoblastic Leukemia
- Interventions
- Drug: Intrathecal Chemotherapy
- Registration Number
- NCT05521087
- Lead Sponsor
- Janssen Research & Development, LLC
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm A: <2 Years Old Dexamethasone Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old Intrathecal Chemotherapy Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old JNJ-75276617 Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Intrathecal Chemotherapy Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old Cytarabine Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old Fludarabine Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old Vincristine Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm A: <2 Years Old Pegaspargase Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Cytarabine Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Fludarabine Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Vincristine Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Dexamethasone Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old Pegaspargase Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617. Arm B: >=2 Years Old JNJ-75276617 Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617.
- Primary Outcome Measures
Name Time Method Number of Participants with AEs by Severity Up to 3 years 5 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. 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.
Number of Participants with Adverse Events (AEs) Up to 3 years 5 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.
Number of Participants with Dose-Limiting Toxicity (DLT) Cycle 1 (28 days) Percentage of participants with DLT will be assessed. The DLTs are specific adverse events related to JNJ-75276617 and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
- Secondary Outcome Measures
Name Time Method Number of Participants with Differentiation of Leukemic Blasts Up to 3 years 5 months Number of participants with differentiation of leukemic blasts will be reported.
Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation Up to 3 years 5 months Changes in expression of menin-histone-lysine N-methyltransferase 2A (KMT2A) target genes or genes associated with differentiation will be reported.
Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Up to 3 years 5 months Percentage of participants who receive an allogeneic HSCT after treatment will be reported.
Time to Response (TTR) Up to 3 years 5 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.
Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML) Up to 3 years 5 months ORR is defined as the percentage of participants who achieve complete response (CR), CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh) per the Response Criteria in AML.
Plasma Concentration of JNJ-75276617 Up to 3 years 5 months Plasma concentration of JNJ-75276617 will be reported.
Number of Participants with Depletion of Leukemic Blasts Up to 3 years 5 months Number of participants with depletion of leukemic blasts will be reported.
Duration of Response (DOR) Up to 3 years 5 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.
Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL) Up to 3 years 5 months ORR in participants with B-cell ALL is defined as the percentage of participants who achieve CR or CRi per the response criteria in B-cell ALL.
Trial Locations
- Locations (22)
Memorial Sloan Kettering
🇺🇸New York, New York, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Lucile Packard Children's Hospital Stanford
🇺🇸Palo Alto, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Children's Wisconsin - Milwaukee Hospital
🇺🇸Milwaukee, Wisconsin, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Lucile Packard Children's Hospital Stanford
🇺🇸Palo Alto, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
UNC Hospitals - N.C. Childrens Hospital
🇺🇸Chapel Hill, North Carolina, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
UNC Hospitals - N.C. Childrens Hospital
🇺🇸Chapel Hill, North Carolina, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Children's Wisconsin - Milwaukee Hospital
🇺🇸Milwaukee, Wisconsin, United States