MOONSHOT (CLL11)
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
Chronic Lymphocytic Leukaemia
The purpose of this study is to evaluate if treatment with epcoritamab will improve outcomes compared with historical value through increased conversion to U-MRD4 (cohort 1) and reduced loss of U-MRD4 (cohort 2) for patients diagnosed with CLL.
Who is it for?
You may be eligible for this study if you are aged 18 and above and have been diagnosed with CLL or SLL
Study details
This is a multi-centre single arm non-randomised phase II study in 2 distinct cohorts of patients:
Cohort 1: Patients that are MRD4+ (defined as >10-4 on peripheral blood samples) at 3 months after completion of Ven-Obin, irrespective of pre-treatment genomics.
Cohort 2: Patients with CLL with adverse-risk genomics (defined as TP53 aberrancy and/or unmutated IGHV) detected before treatment and achieving undetectable MRD4 (U-MRD4) at 3 months following completion of Ven-Obin induction.
Both cohorts will receive the following treatment:
– Epcoritamab will be administered as a subcutaneous injection on a 28-day cycle. In Cycle 1 epcoritamab will be administered on days 1, 8, 15 and 22, following the ramp-up schedule.
– From cycle 2 onwards, epcoritamab will be administered on day 1 of each cycle.
During treatment, patients will have the following assessments :
· Haematology: Haemoglobin, WBC, Platelets
· Biochemistry: Urea, creatinine and electrolytes
· Assess AEs
A total of 38 patients is planned, 14 in cohort 1 and 24 in cohort 2. Each patient will be followed for 4 years post completion of trial treatment, unless withdrawn previously. The total trial duration is expected to be 7 years.
All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.
It is hoped this research will determine if Epcoritamab treatment can improve outcomes for patients diagnosed with CLL.
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
Healthy volunteers: 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.
2. Developed disease progression by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria during or following completion of venetoclax therapy.
Dr. Carolyn Grove
Australasian Leukaemia & Lymphoma Group
Phase 2
CLL11
ACTRN12625000387426