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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04065399




Registration number
NCT04065399
Ethics application status
Date submitted
16/08/2019
Date registered
22/08/2019

Titles & IDs
Public title
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation
Scientific title
A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation
Secondary ID [1] 0 0
2020-004104-34
Secondary ID [2] 0 0
SNDX-5613-0700
Universal Trial Number (UTN)
Trial acronym
AUGMENT-101
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Acute Lymphoblastic Leukemia 0 0
Mixed Lineage Acute Leukemia 0 0
Mixed Phenotype Acute 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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - revumenib
Treatment: Drugs - cobicistat

Experimental: Revumenib - Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms:

* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole
* Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis
* Arm C: Participants receiving revumenib and cobicistat
* Arm D: Participants receiving fluconazole for antifungal prophylaxis
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers
* Arm F: Participants receiving isavuconazole for antifungal prophylaxis

Phase 2: Oral revumenib; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows:

* Cohort 2A: Participants with KMT2Ar ALL/MPAL
* Cohort 2B: Participants with KMT2Ar AML
* Cohort 2C: Participants with NPM1m AML


Treatment: Drugs: revumenib
revumenib orally

Treatment: Drugs: cobicistat
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of dose-limiting toxicities (DLTs) (Phase 1)
Timepoint [1] 0 0
Approximately 1 year
Primary outcome [2] 0 0
Number of participants with treatment-emergent adverse events (TEAEs) (Phase 1)
Timepoint [2] 0 0
Approximately 1 year
Primary outcome [3] 0 0
Cmax (Phase 1)
Timepoint [3] 0 0
Approximately 1 year
Primary outcome [4] 0 0
Tmax (Phase 1)
Timepoint [4] 0 0
Approximately 1 year
Primary outcome [5] 0 0
AUC0-t (Phase 1)
Timepoint [5] 0 0
Approximately 1 year
Primary outcome [6] 0 0
CR+CRh rate (Phase 2)
Timepoint [6] 0 0
Approximately 3 years
Primary outcome [7] 0 0
Number of participants with TEAEs (Phase 2)
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Transfusion independence (Phase 2)
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
CRc rate (Phase 2)
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
ORR (CRc+ morphological leukemia-free state [MLFS] + partial remission [PR]) (Phase 2)
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
TTR (Phase 2)
Timepoint [4] 0 0
Approximately 34 months
Secondary outcome [5] 0 0
DOR (Phase 2)
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
EFS (Phase 2)
Timepoint [6] 0 0
Approximately 3 years
Secondary outcome [7] 0 0
OS (Phase 2)
Timepoint [7] 0 0
Approximately 5 years
Secondary outcome [8] 0 0
Cmax (Phase 2)
Timepoint [8] 0 0
Approximately 3 years
Secondary outcome [9] 0 0
Tmax (Phase 2)
Timepoint [9] 0 0
Approximately 3 years
Secondary outcome [10] 0 0
AUC0-t (Phase 2)
Timepoint [10] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
Participants must have active acute leukemia (bone marrow blasts =5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.

1. Phase 1:

* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
* Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
* Arm C: Participants receiving revumenib in combination with cobicistat.
* Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
* Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
2. Phase 2:

Documented R/R active acute leukemia (bone marrow blasts =5% or reappearance of blasts in peripheral blood) as defined by the NCCN Guidelines® for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
* Cohort 2A: Documented R/R ALL/MPAL with KMT2A rearrangement.
* Cohort 2B: Documented R/R AML with KMT2A rearrangement.
* Cohort 2C: Documented R/R AML with NPM1m.
3. White blood cell count below 25,000/ microliter at time of enrollment. Participants may receive cytoreduction prior to enrollment per protocol-specified criteria.
4. Male or female participants aged =30 days old.
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score =50.
6. Any prior treatment-related toxicities resolved to =Grade 1 prior to enrollment, with the exception of =Grade 2 neuropathy or alopecia.
7. Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or =50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
8. Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
9. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T or NK cell therapy.
10. Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy.
11. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
12. Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
13. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing or cytoreductive therapy.
14. Adequate organ function.
15. If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
Minimum age
30 Days
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants meeting any of the following criteria are not eligible for study participation:

1. Diagnosis of active acute promyelocytic leukemia.
2. Isolated extramedullary relapse (Phase 2 only).
3. Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
4. Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
5. Hepatitis B or C.
6. Pregnant or nursing women.
7. Cardiac Disease:

* Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class =II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
* Corrected QT interval (QTc) >450 milliseconds.
8. Gastrointestinal Disease:

* any gastrointestinal issue of the upper GI tract that might affect oral drug absorption or ingestion (that is, gastric bypass, gastroparesis, etc).
* Cirrhosis with a Child-Pugh score of B or C.
9. Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the participant is not receiving any systemic therapy or radiation.
11. In Phase 1 and Phase 2: Participants requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (for example, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1 and in Phase 2.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
413
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre (PMCC) - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital (RMH) - Parkville
Recruitment hospital [3] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Canada
State/province [17] 0 0
Toronto
Country [18] 0 0
France
State/province [18] 0 0
Pierre-Benite
Country [19] 0 0
France
State/province [19] 0 0
Villejuif
Country [20] 0 0
Germany
State/province [20] 0 0
Essen
Country [21] 0 0
Germany
State/province [21] 0 0
Greifswald
Country [22] 0 0
Germany
State/province [22] 0 0
Gutenberg
Country [23] 0 0
Israel
State/province [23] 0 0
Haifa
Country [24] 0 0
Israel
State/province [24] 0 0
Jerusalem
Country [25] 0 0
Israel
State/province [25] 0 0
Nahariya
Country [26] 0 0
Israel
State/province [26] 0 0
Petach Tikva
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Italy
State/province [28] 0 0
Bologna
Country [29] 0 0
Italy
State/province [29] 0 0
Meldola
Country [30] 0 0
Italy
State/province [30] 0 0
Vicenza
Country [31] 0 0
Lithuania
State/province [31] 0 0
Vilnius
Country [32] 0 0
Netherlands
State/province [32] 0 0
Utrecht
Country [33] 0 0
Spain
State/province [33] 0 0
Hospitalet De Llobregat
Country [34] 0 0
Spain
State/province [34] 0 0
Seville
Country [35] 0 0
Spain
State/province [35] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Syndax Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Angela R Smith, M.D.
Address 0 0
Syndax Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Syndax Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
781-419-1400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04065399