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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04951778




Registration number
NCT04951778
Ethics application status
Date submitted
23/06/2021
Date registered
7/07/2021

Titles & IDs
Public title
Study to Evaluate Safety and Tolerability of CC-91633 (BMS-986397) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Scientific title
A Phase 1, Open-label, Dose-finding Study of CC-91633 (BMS-986397) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Secondary ID [1] 0 0
2020-005329-95
Secondary ID [2] 0 0
CC-91633-AML-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute 0 0
Myelodysplastic Syndromes 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
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
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 - CC-91633

Experimental: Participants with R/R AML and R/R HR-MDS - Part A - Part A (Dose Escalation) of the study will enroll R/R AML (Relapsed or Refractory Acute Myeloid Leukemia) and R/R HR-MDS (Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes) participants and will evaluate the safety and tolerability of escalating doses of CC-91633, administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 doses (RP2D) and schedule.

Experimental: Participants with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) - Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R AML participants.

Experimental: Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS) - Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R HR-MDS participants.


Treatment: Drugs: CC-91633
Administered orally according to the assigned treatment schedule

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [1] 0 0
Up to 2 years
Primary outcome [2] 0 0
Dose-limiting Toxicity (DLT)
Timepoint [2] 0 0
Up to 42 days after first dose of study treatment in Part A
Primary outcome [3] 0 0
Incidence of Adverse Events (AEs)
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Complete Remission Rate (CRR)
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Minimal residual disease negative complete remission rate (CRRMRD-)
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Combined Complete Remission Rate (cCRR)
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Morphologic Leukemia-free State Rate (MLFSR)
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Partial Remission Rate (PRR)
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Stable Disease Rate (SDR)
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Progression-free Survival (PFS) rate at 3 and 9 months
Timepoint [7] 0 0
At 3 months and 9 months of PFS
Secondary outcome [8] 0 0
Overall Survival (OS) rate
Timepoint [8] 0 0
At 6 and 12 months of survival
Secondary outcome [9] 0 0
Overall Response Rate (ORR)
Timepoint [9] 0 0
Up to 4 years
Secondary outcome [10] 0 0
Overall Survival (OS)
Timepoint [10] 0 0
Up to 4 years
Secondary outcome [11] 0 0
Relapse-free Survival (RFS)
Timepoint [11] 0 0
Up to 4 years
Secondary outcome [12] 0 0
Progression-free Survival (PFS)
Timepoint [12] 0 0
Up to 4 years
Secondary outcome [13] 0 0
Event-free Survival (EFS)
Timepoint [13] 0 0
Up to 4 years
Secondary outcome [14] 0 0
Duration of remission/response
Timepoint [14] 0 0
Up to 4 years
Secondary outcome [15] 0 0
Time to remission/response
Timepoint [15] 0 0
Up to 4 years
Secondary outcome [16] 0 0
Efficacy: Time to transformation to Acute Myeloid Leukemia (AML) for High-Risk Myelodysplastic Syndrome (HR-MDS)
Timepoint [16] 0 0
Up to 4 years
Secondary outcome [17] 0 0
CC-91633 Pharmacokinetics - Cmax
Timepoint [17] 0 0
Up to 4 years
Secondary outcome [18] 0 0
CC-91633 Pharmacokinetics - AUC(0-T)
Timepoint [18] 0 0
Up to 4 years
Secondary outcome [19] 0 0
CC-91633 Pharmacokinetics - AUC(TAU)
Timepoint [19] 0 0
Up to 4 years
Secondary outcome [20] 0 0
CC-91633 Pharmacokinetics - Tmax
Timepoint [20] 0 0
Up to 4 years
Secondary outcome [21] 0 0
CC-91633 Pharmacokinetics - T-HALF
Timepoint [21] 0 0
Up to 4 years
Secondary outcome [22] 0 0
CC-91633 Pharmacokinetics - CLT/F
Timepoint [22] 0 0
Up to 4 years
Secondary outcome [23] 0 0
CC-91633 Pharmacokinetics - Vz/F
Timepoint [23] 0 0
Up to 4 years
Secondary outcome [24] 0 0
CC-2004772 Pharmacokinetics - Cmax
Timepoint [24] 0 0
Up to 4 years
Secondary outcome [25] 0 0
CC-2004772 Pharmacokinetics - AUC(0-T)
Timepoint [25] 0 0
Up to 4 years
Secondary outcome [26] 0 0
CC-2004772 Pharmacokinetics - AUC(TAU)
Timepoint [26] 0 0
Up to 4 years
Secondary outcome [27] 0 0
CC-2004772 Pharmacokinetics - Tmax
Timepoint [27] 0 0
Up to 4 years
Secondary outcome [28] 0 0
CC-2004772 Pharmacokinetics - T-HALF
Timepoint [28] 0 0
Up to 4 years
Secondary outcome [29] 0 0
CC-2004772 Pharmacokinetics - CLT/F
Timepoint [29] 0 0
Up to 4 years
Secondary outcome [30] 0 0
CC-2004772 Pharmacokinetics - Vz/F
Timepoint [30] 0 0
Up to 4 years

Eligibility
Key inclusion criteria
Participants must satisfy the criteria below to be enrolled in the Dose Escalation (Part A) or the Dose Expansion (Part B) of this study.

* Participant is = 18 years of age, at the time of signing the ICF.
* Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
* Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
* Relapsed or refractory acute myeloid leukemia (R/R AML) and relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) as defined by the World Health Organization (WHO) criteria who have failed or are ineligible for all available therapies which may provide clinical benefit
* Participant has Eastern Cooperative Oncology Group Performance Status of 0 to 2.
* Participants must have the following screening laboratory values:

* Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion.
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) = 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be = 5.0 x ULN.
* Uric acid = 7.5 mg/dL (446 µmol/L).
* Serum total bilirubin = 1.5 x ULN, unless considered due to Gilbert's syndrome
* Estimated serum creatinine clearance of = 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
* INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The presence of any of the following will exclude a participant from enrollment:

* Participant has any condition, including active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant were to participate in the study.
* Any other significant medical condition, laboratory abnormality, or psychiatric illness which places the participant at unacceptable risk if he/she were to participate in the study or that would prevent the participant from complying with the study.
* Participant has any condition that confounds the ability to interpret data from the study.
* Participants with acute promyelocytic leukemia.
* Participants with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
* Participants with immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation.
* Participants with impaired cardiac function or clinically significant cardiac diseases,
* Participants who have undergone major surgery = 2 weeks prior to starting CC-91633. Participants must have recovered from any clinically significant effects of recent surgery.
* Pregnant or nursing individuals.
* Participants with known human immunodeficiency virus infection.
* Participants with known chronic, active hepatitis B virus or hepatitis C virus C (HCV) infection.
* Participants with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
* Participants with history of concurrent second cancers requiring active, ongoing systemic treatment
* Participants with clinically significant diarrhea, vomiting or malabsorption felt to limit absorption of orally administered medications.
* Participants with known or suspected hypersensitivity to any of the components or excipients of the study treatment or to similar class drugs (eg, lenalidomide).

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 604 - Adelaide
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Local Institution - 603 - Melbourne
Recruitment hospital [6] 0 0
St Vincent's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
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
Pennsylvania
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
Washington
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Sevilla
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Greater Manchester
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London, City Of
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Leeds
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Oxford

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
See Plan Description
Available to whom?
See Plan Description
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/


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.