Leukemia, Myeloid, AcutePhase 1NCT04336982
A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia
A Phase 1 study testing CC-90009, Venetoclax and Azacitidine in people with Leukemia, Myeloid, Acute, run by Celgene at 14 sites in 5 countries.
Trial summary
CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- CC-90009, Venetoclax and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 5 Aug 2020to 5 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Arm A (CC-90009 + venetoclax/azacitidine):
- Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is either ≥ 75 years of age or is ineligible for intensive chemotherapy OR
- Part A: Primary Refractory AML, or AML in first relapse, and is ≥ 18 years of age
- Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible
- Arm B (CC-90009 + gilteritinib):
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- Subject is ≥ 18 years of age.
- Fms-like tyrosine kinase 3 (FLT3) mutation positive.
- Gilteritinib treatment naïve
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Subject must have the following screening laboratory values:
- Total White Blood Cell count (WBC) < 25 x 10^9/L prior to study treatments. Treatment with hydroxyurea to achieve this level is allowed.
- Selected electrolytes within normal limits or correctable with supplements.
- Participant must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) and bilirubin ≤ 1.5 x ULN
- Participant has adequate renal function as demonstrated by an estimated serum creatinine clearance of ≥ 30 mL/min.
- Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.
Who cannot join
- Subject with acute promyelocytic leukemia (APL)
- Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment
- Patients with prior autologous hematopoietic stem cell transplant (HSCT) who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (eg, transplant related side effects)
- Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing
- Subject on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted
- Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2
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- Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
- Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
- Complete left bundle branch or bifascicular block.
- Congenital long QT syndrome.
- Persistent or clinically meaningful ventricular arrhythmias.
- QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)
- Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.
- Cardiovascular disability status of New York Heart Association Class ≥2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
- Subject is a pregnant or lactating female
- Additional exclusion criteria based on combination agent:
- For Combination Arm A (venetoclax/azacitidine):
- Received strong or moderate CYP3A inhibitors or inducers or P-gp inhibitors within 7 days prior to initiation of first venetoclax dose.
- Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to first venetoclax dose through last dose of venetoclax.
- Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
- Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment.
- Previous SARS-CoV-2 vaccine within 14 days of C1D1.
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
United States7 sites
Local Institution - 103
Boston, Massachusetts, 02115
Local Institution - 108
Hackensack, New Jersey, 07601
Local Institution - 105
Houston, Texas, 77030-4009
Local Institution - 107
New Haven, Connecticut, 06510
Local Institution - 104
San Francisco, California, 94143-0324
Local Institution - 102
Seattle, Washington, 98109-1024
Local Institution - 101
St Louis, Missouri, 63110
France3 sites
Local Institution - 402
Marseille, 13273
Local Institution - 401
Pessac, 33604
Local Institution - 404
Toulouse, 31059
Canada2 sites
Local Institution - 202
Edmonton, Alberta, T6G 2R7
Local Institution - 201
Toronto, Ontario, M5G 2M9
About this study
Official title: An Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML).
Read the detailed description
Study CC-90009-AML-002 is an open-label, multi-arm, parallel multi-cohort, multicenter, Phase 1b study to determine the safety, tolerability, PK, and efficacy of CC 90009 in combination with anti-leukemia agents used for the treatment of AML. CC 90009 will be given as a combination therapy to subjects with newly diagnosed (ND) or relapsed or refractory (R/R) AML.
The dose and schedule finding part (Part A) of the study will evaluate the safety, PK and PD data, and preliminary efficacy information and determine the Part B dose and schedule for each arm.
The expansion part (Part B) of the study will further evaluate the safety and efficacy of the CC-90009 containing combination at or below the maximum tolerated dose (MTD) in the selected cohorts in order to determine the recommended Phase 2 dose (RP2D) for subjects with AML.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- CC-90009, Venetoclax, Azacitidine, Gilteritinib
- Keywords
- CC-90009, Venetoclax, Azacitidine, Gilteritinib, Hematologic cancers, Leukemia, Acute myeloid leukemia, AML
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-90009Drug
Injection
VenetoclaxDrug
Tablet
AzacitidineDrug
Injection
GilteritinibDrug
Tablet
| Study group | Role | What they receive |
|---|---|---|
| CC-90009 in combination with venetoclax and azacitidine | Experimental | CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD.
Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle. Receives: Drug: CC-90009; Drug: Venetoclax; Drug: Azacitidine |
| CC-90009 in combination with gilteritinib | Experimental | CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD. Receives: Drug: Gilteritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Number of participants with a DLT
Measured: Up to 28 days
Adverse Events (AEs)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology.
Measured: Up to 28 days after last dose of study drug.
Secondary outcomes (9)
Complete Remission Rate (CRR),
is defined as the rate for any type of CR or CRh
Measured: Up to 3 years
Objective Response Rate (ORR)
includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR)
Measured: Up to 3 years
Progression Free Survival (PFS)
is defined as the time from the first dose of study drug(s) to the first occurrence of relapse or progression or death from any cause
Measured: Up to 3 years
Overall Survival (OS)
is measured as the time from the first dose of study drug(s) to death due to any cause and will be analyzed in a manner similar to that described for PFS.
Measured: Up to 3 years
Duration of Remission
is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded) until the first date at which relapse, or progressive disease is objectively documented.
Measured: Up to 3 years
Time to Remission
is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded)
Measured: Up to 3 years
Pharmacokinetics - Cmax
observed maximum concentration in plasma
Measured: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Pharmacokinetics - AUC24
area under the plasma concentration time-curve from time 0 to 24 hours postdose
Measured: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Pharmacokinetics - t1/2
terminal half life
Measured: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2020
- Study start5 Aug 2020
- Primary completion25 Oct 2023
- Study completion5 Apr 2024
Why it stopped: Business objectives have changed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04336982
- Sponsor's protocol ID
- CC-90009-AML-002
- Other IDs
- U1111-1247-5619, 2019-001681-15, 2019
- Status last verified
- May 2024
- First submitted
- 26 Mar 2020
- Last updated
- 31 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
Publications
Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C, Fontanillo C, Tran E, Contreras A, Ng SWK, Matyskiela M, Wang K, Chamberlain P, Cathers B, Carmichael J, Hansen J, Wang JCY, Minden MD, Fan J, Pierce DW, Pourdehnad M, Rolfe M, Lopez-Girona A, Dick JE, Lu G. CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells. Blood. 2021 Feb 4;137(5):661-677. doi: 10.1182/blood.2020008676.
PubMed 33197925
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT04336982
- Acronym / sponsor ID
- CC-90009-AML-002
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- CC-90009, Venetoclax, Azacitidine, Gilteritinib, Hematologic cancers, Leukemia, Acute myeloid leukemia, AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business objectives have changed.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- AbbVie
- Study start
- 5 Aug 2020 (actual)
- Primary completion
- 25 Oct 2023 (actual)
- Study completion
- 5 Apr 2024 (actual)
- First posted
- 7 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML).
Detailed description
Study CC-90009-AML-002 is an open-label, multi-arm, parallel multi-cohort, multicenter, Phase 1b study to determine the safety, tolerability, PK, and efficacy of CC 90009 in combination with anti-leukemia agents used for the treatment of AML. CC 90009 will be given as a combination therapy to subjects with newly diagnosed (ND) or relapsed or refractory (R/R) AML.
The dose and schedule finding part (Part A) of the study will evaluate the safety, PK and PD data, and preliminary efficacy information and determine the Part B dose and schedule for each arm.
The expansion part (Part B) of the study will further evaluate the safety and efficacy of the CC-90009 containing combination at or below the maximum tolerated dose (MTD) in the selected cohorts in order to determine the recommended Phase 2 dose (RP2D) for subjects with AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CC-90009 in combination with venetoclax and azacitidine | Experimental | Drug: CC-90009, Drug: Venetoclax, Drug: AzacitidineCC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD. Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle. |
| CC-90009 in combination with gilteritinib | Experimental | Drug: GilteritinibCC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Arm A (CC-90009 + venetoclax/azacitidine):
- Arm B (CC-90009 + gilteritinib):
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Subject must have the following screening laboratory values:
Key exclusion criteria (24 listed)
- Subject with acute promyelocytic leukemia (APL)
- Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment
- Patients with prior autologous hematopoietic stem cell transplant (HSCT) who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (eg, transplant related side effects)
- Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing
- Subject on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-90009Injection | Drug | CC-90009 in combination with venetoclax and azacitidine |
| VenetoclaxTablet | Drug | CC-90009 in combination with venetoclax and azacitidine |
| AzacitidineInjection | Drug | CC-90009 in combination with venetoclax and azacitidine |
| GilteritinibTablet | Drug | CC-90009 in combination with gilteritinib |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: Up to 28 days
Number of participants with a DLT
Adverse Events (AEs)
Time frame: Up to 28 days after last dose of study drug.
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology.
9 secondary outcomes
Complete Remission Rate (CRR),
Time frame: Up to 3 years
Objective Response Rate (ORR)
Time frame: Up to 3 years
Progression Free Survival (PFS)
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Duration of Remission
Time frame: Up to 3 years
Time to Remission
Time frame: Up to 3 years
Pharmacokinetics - Cmax
Time frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Pharmacokinetics - AUC24
Time frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Pharmacokinetics - t1/2
Time frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Results and safety
The study was stopped early (reason given: Business objectives have changed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2024.
- Derived from this study: PubMed 33197925Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C, Fontanillo C, Tran E, Contreras A, Ng SWK, Matyskiela M, Wang K, Chamberlain P, Cathers B, Carmichael J, Hansen J, Wang JCY, Minden MD, Fan J, Pierce DW, Pourdehnad M, Rolfe M, Lopez-Girona A, Dick JE, Lu G. CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells. Blood. 2021 Feb 4;137(5):661-677. doi: 10.1182/blood.2020008676.
- BMS Clinical Trial InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-90009, Venetoclax and Azacitidine in people with Leukemia, Myeloid, Acute, run by Celgene at 14 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, France, Canada, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business objectives have changed.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04336982, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2024.