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Trial registered on ANZCTR


Registration number
ACTRN12625000387426p
Ethics application status
Not yet submitted
Date submitted
25/09/2024
Date registered
1/05/2025
Date last updated
1/05/2025
Date data sharing statement initially provided
1/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
CLL11 - A study to evaluate the efficacy of Epcoritamab consolidation in high genomic risk and Measurable Residual Disease (MRD)-positive Chronic Lymphocytic Leukaemia (CLL) patients after first-line venetoclax and obinutuzumab
Scientific title
CLL11 - An ALLG phase II trial of Epcoritamab consolidation in high genomic risk and MRD-positive Chronic Lymphocytic Leukaemia (CLL) patients after first-line venetoclax and obinutuzumab
Secondary ID [1] 312933 0
None
Universal Trial Number (UTN)
Trial acronym
MOONSHOT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukaemia 335100 0
Condition category
Condition code
Cancer 331602 331602 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Epcoritamab is supplied as a concentrate for solution for intended subcutaneous injection. Epcoritamab will be provided by AbbVie as 4mg/0.8mL and 48mg/0.8mL vials.

As per standard of care (SOC) practices, patients will receive induction therapy of 12 cycles with venetoclax and obinutuzumab (Ven-Obi) as directed by their care provider. Eligible patients will be registered to the CLL11 trial prior to an Measurable Residual Disease (MRD) assessment, which will be performed 12-24 weeks post-completion of Ven-O.
For clarity, Ven-Obi treatment is available as SOC and is not a part of the CLL11 Moonshot Trial treatment schedule.

Epcoritamab will be administered as a subcutaneous injection on a 28-day cycle. In Cycle 1 epcoritamab will be administered on day 1 (0.16 mg), day 8 (0.8 mg), day 15 (3.0 mg) and 22 (48mg) as a standard dose-escalation cycle, From cycle 2 onwards, epcoritamab will be administered on day 1 of every cycle at a fixed dose of 48mg for 11 cycles after (until cycle 12).

Both patient cohorts will be given the same treatment and all treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.

The approximate duration of study participation for patients is a maximum of 5 years (1 year treatment, 4 years follow up)
Intervention code [1] 329467 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339342 0
Cohort 1 primary outcome is to evaluate the proportion of patients who achieve (undetectable minimal residual disease) U-MRD4 after 6 months of epcoritamab treatment.
Timepoint [1] 339342 0
Samples from patients in cohort 1 will be collected at at screening and cycle 7 day 1 (C7D1 i,e, after 6 months of epcoritamab treatment). The endpoint analysis will occur when all patients in cohort 1 have completed 6months of treatment and had the cycle 7, day 1 sample collected.
Primary outcome [2] 339343 0
Cohort 2 primary outcome is to evaluate the proportion of patients who convert from MRD4 to MRD4 positivity by 2 years after commencing epcoritamab.
Timepoint [2] 339343 0
Samples from patients in cohort 2 will be collected at at screening and 2 years after commencing of epcoritamab treatment. The endpoint analysis will occur when all patients in cohort 2 have completed 2 years.
Secondary outcome [1] 439584 0
Progression Free Survival (PFS)
Timepoint [1] 439584 0
PFS for cohort 1 will be at 2 and 4 years post commencement of epcoritamab PFS for cohort 2: at 4 years (post commencement of epcoritamab) Patient data for cohort 1 and 2 will be pooled for the 4 year analysis.
Secondary outcome [2] 439585 0
Conversion to U-MRD6 (in patients who were MRD6+ prior to epcoritamab). MRD6+ defined as 10^-6 sensitivity by Clonoseq assay)
Timepoint [2] 439585 0
Assessed at screening, cycle 2 day 1, cycle 7 day 1 (after 6 months of epcoritamab treatment) and at end of trial (end of cycle 12). This endpoint will be assessed for patients in cohort 1 and cohort 2 at the same time and data will be pooled.
Secondary outcome [3] 439586 0
The rate of grade 3 (or higher) adverse events (AEs) after 12 cycles of epcoritamab.
Timepoint [3] 439586 0
Adverse events of special interest will be the rate of cytokine release syndrome during the first 4 weeks of epcoritamab and the rate of grade 3 or higher infections within the first 2 years after starting epcoritamab. Data will be collected from medical records for both cohorts of patients and pooled for analysis.
Secondary outcome [4] 439587 0
Time to conversion to MRD4 positivity in patients who achieve U-MRD4
Timepoint [4] 439587 0
Assessed at screening, cycle 2 day 1, cycle 7 day 1 (after 6 months of epcoritamab treatment) and at end of trial (end of cycle 12). This endpoint will be assessed for patients in cohort 1 and cohort 2 at the same time and data will be pooled.
Secondary outcome [5] 439591 0
Overall Survival (OS)
Timepoint [5] 439591 0
OS for cohort 1 will be at 2 and 4 years post commencement of epcoritamab OS for cohort 2: at 4 years (post commencement of epcoritamab) Patient data for cohort 1 and 2 will be pooled for the 4 year analysis.

Eligibility
Key inclusion criteria
All of the following criteria must be satisfied for enrolment into the trial by patients in both cohort groups, except where noted in criteria number 1. .

1. Patients must have a diagnosis of CLL or SLL (Cohort 1 and 2)

and

EITHER

Have MRD, with greater than or equal to 0.01 percent CLL cells in peripheral blood, measured 12-24 weeks post-completion of venetoclax, regardless of pre-treatment genomic features (Cohort 1).

OR
Have undetectable MRD (U-MRD4), measured 12-24 weeks post-completion of venetoclax, but have high-risk cytogenetic or molecular features, defined as at least one of: del(17p), del(11q), mutated TP53, complex metaphase karyotype (defined as greater than or equal to 5 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis), or unmutated IGHV. These features could have been demonstrated from a sample taken at any time prior to or during treatment with Ven-Obi (Cohort 2).

2. Patients must have received first-line therapy with Ven-Obi and must have been able to tolerate 12 months of venetoclax therapy at a dose of greater than or equal to 100mg per day
AND
Have received no other CLL-directed therapy except local palliative radiotherapy or corticosteroids alone for autoimmune complications.
3. Age 18 years or older.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
5. Patients must have adequate renal and hepatic function:
- Serum bilirubin less than or equal to 1.5 times upper limit of normal (ULN) or less than or equal to 3 times ULN for patients with Gilbert’s syndrome.
- Serum creatinine clearance of greater than 45ml per min (calculated or measured).
- ALT and AST less than or equal to 3.0 times ULN.
6. Adequate bone marrow function:
- Platelet count of greater than 75 x 10^9 per Liter, with no platelet transfusion in prior 4 weeks.
- ANC greater than or equal to 1.5 times 10^9 per L in the absence of growth factor support.
- Hemoglobin greater than or equal to 100g per L, with no red cell transfusion in the prior 4 weeks.
7. Adequate cardiac function, as assessed by:
- Absence of uncontrolled cardiac arrhythmia.
- New York Heart Association (NYHA) functional class less than or equal to 1.
8. Ability to provide informed consent and adhere to the required follow-up.
9. Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (Beta-hCG) pregnancy test result at screening and prior to day 1 of each dose of study drug and must agree to use both a highly effective method of birth control during the period of therapy and for 1 year after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for greater than or equal to 1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who are sexually active with a woman of childbearing potential must agree to use effective contraception, defined above, during the study and for 1 year following the last dose of study drug.
10. Women must agree not to donate eggs and men must agree not to donate sperm for 12 months after the last dose of epcoritamab.
11. Patients or their legally authorised representative must provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Received prior systemic therapy for CLL/SLL.
2. Developed disease progression by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria during or following completion of venetoclax therapy.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
This is a multi-centre single arm non-randomised phase II study with 2 cohorts of patients who will receive the same treatment and undergo the same assessments. The trial primary endpoints are per each cohort, with all other endpoints being analyse with pooled data.

The primary endpoint of cohort 1 is to evaluate the proportion of MRD+ patients who achieve U-MRD4 in peripheral blood after 6 months of epcoritamab treatment. The primary endpoint of cohort 2 is to evaluate the proportion of patients who convert to MRD4+ by 2 years after commencing epcoritamab.



Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/06/2025
Actual
Date of last participant enrolment
Anticipated
2/06/2027
Actual
Date of last data collection
Anticipated
2/06/2032
Actual
Sample size
Target
38
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 26553 0
New Zealand
State/province [1] 26553 0

Funding & Sponsors
Funding source category [1] 317367 0
Other Collaborative groups
Name [1] 317367 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 317367 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
Country
Australia
Secondary sponsor category [1] 319655 0
None
Name [1] 319655 0
Address [1] 319655 0
Country [1] 319655 0
Other collaborator category [1] 283185 0
Individual
Name [1] 283185 0
Professor Stephen Opat (Co-Chief Investigator)
Address [1] 283185 0
Country [1] 283185 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 316097 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 316097 0
Ethics committee country [1] 316097 0
Australia
Date submitted for ethics approval [1] 316097 0
02/05/2025
Approval date [1] 316097 0
Ethics approval number [1] 316097 0

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

Contacts
Principal investigator
Name 136766 0
Prof Stephen Opat
Address 136766 0
Monash Health, 246 Clayton Road, Clayton VIC 3168
Country 136766 0
Australia
Phone 136766 0
+61 3 9594 4366
Fax 136766 0
Email 136766 0
[email protected]
Contact person for public queries
Name 136767 0
Delaine Smith
Address 136767 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 136767 0
Australia
Phone 136767 0
+61 3 8373 9701
Fax 136767 0
Email 136767 0
[email protected]
Contact person for scientific queries
Name 136768 0
Delaine Smith
Address 136768 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 136768 0
Australia
Phone 136768 0
+61 3 8373 9701
Fax 136768 0
Email 136768 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply that the requester must agree to before access is granted

Conditions for requesting access:
• -

What individual participant data might be shared?
• De-identified IPD data for all data collected during the trial

What types of analyses could be done with individual participant data?
• Any type of analysis
Assessed on a case-by-case basis


When can requests for individual participant data be made (start and end dates)?
From:
Data available 3 months following publication, for an indefinite period

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]


Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24215Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]


Results publications and other study-related documents

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