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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05521087




Registration number
NCT05521087
Ethics application status
Date submitted
29/08/2022
Date registered
30/08/2022
Date last updated
9/11/2023

Titles & IDs
Public title
A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias
Scientific 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
Secondary ID [1] 0 0
2022-000380-46
Secondary ID [2] 0 0
CR109192
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Leukemias 0 0
Acute Myeloid Leukemia 0 0
Acute Lymphoblastic Leukemia 0 0
Acute Leukemia of Ambiguous Lineage 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-75276617
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cytarabine
Treatment: Drugs - Intrathecal Chemotherapy
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Vincristine
Treatment: Drugs - Pegaspargase

Experimental: Arm A: <2 Years Old - 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.

Experimental: Arm B: >=2 Years Old - 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.


Treatment: Drugs: JNJ-75276617
JNJ-75276617 will be administered orally.

Treatment: Drugs: Fludarabine
Fludarabine chemotherapy will be administered as intravenous (IV) infusion for participants with AML.

Treatment: Drugs: Cytarabine
Cytarabine chemotherapy will be administered as IV infusion for participants with AML.

Treatment: Drugs: Intrathecal Chemotherapy
Intrathecal chemotherapy will be administered as IV infusion for participants with AML or B-cell ALL.

Treatment: Drugs: Dexamethasone
Dexamethasone chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Treatment: Drugs: Vincristine
Vincristine chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Treatment: Drugs: Pegaspargase
Pegaspargase chemotherapy will be administered as IV infusion for participants with B-cell ALL.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to 3 years 5 months
Primary outcome [2] 0 0
Number of Participants with AEs by Severity
Timepoint [2] 0 0
Up to 3 years 5 months
Primary outcome [3] 0 0
Number of Participants with Dose-Limiting Toxicity (DLT)
Timepoint [3] 0 0
Cycle 1 (28 days)
Secondary outcome [1] 0 0
Plasma Concentration of JNJ-75276617
Timepoint [1] 0 0
Up to 3 years 5 months
Secondary outcome [2] 0 0
Number of Participants with Depletion of Leukemic Blasts
Timepoint [2] 0 0
Up to 3 years 5 months
Secondary outcome [3] 0 0
Number of Participants with Differentiation of Leukemic Blasts
Timepoint [3] 0 0
Up to 3 years 5 months
Secondary outcome [4] 0 0
Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation
Timepoint [4] 0 0
Up to 3 years 5 months
Secondary outcome [5] 0 0
Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)
Timepoint [5] 0 0
Up to 3 years 5 months
Secondary outcome [6] 0 0
Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL)
Timepoint [6] 0 0
Up to 3 years 5 months
Secondary outcome [7] 0 0
Time to Response (TTR)
Timepoint [7] 0 0
Up to 3 years 5 months
Secondary outcome [8] 0 0
Duration of Response (DOR)
Timepoint [8] 0 0
Up to 3 years 5 months
Secondary outcome [9] 0 0
Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Timepoint [9] 0 0
Up to 3 years 5 months

Eligibility
Key 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
Minimum age
30 Days
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
7/02/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/09/2026
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
France
State/province [11] 0 0
Lille
Country [12] 0 0
France
State/province [12] 0 0
Lyon Cedex 08
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Rennes Cedex 2
Country [15] 0 0
France
State/province [15] 0 0
Toulouse
Country [16] 0 0
France
State/province [16] 0 0
Vandœuvre-lès-Nancy
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Hamburg
Country [20] 0 0
Germany
State/province [20] 0 0
Hannover
Country [21] 0 0
Germany
State/province [21] 0 0
Munchen
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Zaragoza
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Birmingham
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Glasgow
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05521087
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
Participate-In-This-Study@its.jnj.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05521087