Back to resultsA Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias
Primary Purpose
Acute Leukemias, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
Status
Not yet recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JNJ-75276617
Fludarabine
Cytarabine
Intrathecal Chemotherapy
Dexamethasone
Vincristine
Pegaspargase
Sponsored by
About this trial
This is an interventional treatment trial for Acute Leukemias
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)
Sites / Locations
- University of Alabama at Birmingham
- City of Hope National Medical Center
- Dana-Farber Cancer Institute
- Memorial Sloan Kettering
- UNC Hospitals - N.C. Childrens Hospital
- Atrium Health
- Cincinnati Children's Hospital Medical Center
- St Jude Children's Research Hospital
- MD Anderson Cancer Center
- University of Utah
- Children's Wisconsin - Milwaukee Hospital
- Hôpital Jeanne de Flandre
- Institut D'Hematologie Et D'Oncologie Pediatrique
- Hôpital trousseau- APHP
- Hôpital Robert Debré
- CHU de Rennes - Hôpital Sud
- CHU de Toulouse Hopital des Enfants
- Centre Hospitalier Universitaire de Nancy - Hôpital Central
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
- Universitatsklinikum Essen
- Universitaetsklinik Hamburg-Eppendorf
- Medizinische Hochschule Hannover
- Dr. Von Haunersches Kinderspital der Universitaet Muenchen
- Hosp. Univ. Vall D Hebron
- Hosp. Infantil Univ. Niño Jesus
- Hosp. Univ. Miguel Servet
- Birmingham Children's Hospital
- Royal Hospital for Sick Children
- University College London Hospitals
- Great Ormond Street Hospital
- Royal Marsden Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: <2 Years Old
Arm B: >=2 Years Old
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events (AEs)
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 AEs by Severity
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 Dose-Limiting Toxicity (DLT)
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
Plasma Concentration of JNJ-75276617
Plasma concentration of JNJ-75276617 will be reported.
Number of Participants with Depletion of Leukemic Blasts
Number of participants with depletion of leukemic blasts will be reported.
Number of Participants with Differentiation of Leukemic Blasts
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
Changes in expression of menin-histone-lysine N-methyltransferase 2A (KMT2A) target genes or genes associated with differentiation will be reported.
Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)
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.
Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL)
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.
Time to Response (TTR)
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.
Duration of Response (DOR)
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.
Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Percentage of participants who receive an allogeneic HSCT after treatment will be reported.
Full Information
NCT ID
NCT05521087
First Posted
August 29, 2022
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05521087
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 7, 2024 (Anticipated)
Primary Completion Date
September 11, 2026 (Anticipated)
Study Completion Date
September 11, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemias, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Acute Leukemia of Ambiguous Lineage
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A: <2 Years Old
Arm Type
Experimental
Arm Description
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 Title
Arm B: >=2 Years Old
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
JNJ-75276617
Intervention Description
JNJ-75276617 will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine chemotherapy will be administered as intravenous (IV) infusion for participants with AML.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Cytarabine chemotherapy will be administered as IV infusion for participants with AML.
Intervention Type
Drug
Intervention Name(s)
Intrathecal Chemotherapy
Intervention Description
Intrathecal chemotherapy will be administered as IV infusion for participants with AML or B-cell ALL.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone chemotherapy will be administered as IV infusion for participants with B-cell ALL.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Vincristine chemotherapy will be administered as IV infusion for participants with B-cell ALL.
Intervention Type
Drug
Intervention Name(s)
Pegaspargase
Intervention Description
Pegaspargase chemotherapy will be administered as IV infusion for participants with B-cell ALL.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
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.
Time Frame
Up to 3 years 5 months
Title
Number of Participants with AEs by Severity
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. 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.
Time Frame
Up to 3 years 5 months
Title
Number of Participants with Dose-Limiting Toxicity (DLT)
Description
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.
Time Frame
Cycle 1 (28 days)
Secondary Outcome Measure Information:
Title
Plasma Concentration of JNJ-75276617
Description
Plasma concentration of JNJ-75276617 will be reported.
Time Frame
Up to 3 years 5 months
Title
Number of Participants with Depletion of Leukemic Blasts
Description
Number of participants with depletion of leukemic blasts will be reported.
Time Frame
Up to 3 years 5 months
Title
Number of Participants with Differentiation of Leukemic Blasts
Description
Number of participants with differentiation of leukemic blasts will be reported.
Time Frame
Up to 3 years 5 months
Title
Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation
Description
Changes in expression of menin-histone-lysine N-methyltransferase 2A (KMT2A) target genes or genes associated with differentiation will be reported.
Time Frame
Up to 3 years 5 months
Title
Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)
Description
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.
Time Frame
Up to 3 years 5 months
Title
Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL)
Description
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.
Time Frame
Up to 3 years 5 months
Title
Time to Response (TTR)
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.
Time Frame
Up to 3 years 5 months
Title
Duration of Response (DOR)
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.
Time Frame
Up to 3 years 5 months
Title
Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Description
Percentage of participants who receive an allogeneic HSCT after treatment will be reported.
Time Frame
Up to 3 years 5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Days
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
UNC Hospitals - N.C. Childrens Hospital
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
St Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Children's Wisconsin - Milwaukee Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hôpital Jeanne de Flandre
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Institut D'Hematologie Et D'Oncologie Pediatrique
City
Lyon Cedex 08
ZIP/Postal Code
69008
Country
France
Facility Name
Hôpital trousseau- APHP
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hôpital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
CHU de Rennes - Hôpital Sud
City
Rennes Cedex 2
ZIP/Postal Code
35200
Country
France
Facility Name
CHU de Toulouse Hopital des Enfants
City
Toulouse
ZIP/Postal Code
31300
Country
France
Facility Name
Centre Hospitalier Universitaire de Nancy - Hôpital Central
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitaetsklinik Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Dr. Von Haunersches Kinderspital der Universitaet Muenchen
City
Munchen
ZIP/Postal Code
80337
Country
Germany
Facility Name
Hosp. Univ. Vall D Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hosp. Infantil Univ. Niño Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hosp. Univ. Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Royal Hospital for Sick Children
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
University College London Hospitals
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias
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