Safety and Efficacy Study of Epcoritamab in Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter’s Syndrome
- Conditions
- Chronic Lymphocytic LeukemiaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000848-57-NL
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 171
All Subjects
• Subject must sign an ICF, prior to any Screening procedures
• Must be at least 18 years of age
• ECOG performance status score of 0,1 or 2
• Evidence of CD20 positivity in a sample representative of the disease (eg, tumor biopsy/peripheral blood/bone arrow) at Screening
• Has acceptable laboratory parameters
• A woman with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of epcoritamab.
• A woman of childbearing potential must have a negative serum (beta-hCG) pregnancy test at Screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle.
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after last treatment.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
Inclusion Criteria Specific to Subjects With R/R CLL– Dose Escalation Monotherapy (All Cohorts) and Expansion Monotherapy (Arm 1)
• Must have active CLL/SLL disease that needs treatment.
• R/R CLL after receiving at least 2 prior lines of therapy.
• Diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek et al., 2018a)
• Must take prophylaxis for TLS
Inclusion Criteria Specific to Subjects With Richter’s Syndrome – Expansion Monotherapy Arm 2A
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or MRI)
• Must provide a mandatory FFPE tumor tissue sample;
Inclusion Criteria Specific to Subjects With Richter’s Syndrome – Lenalidomide Combination Therapy Expansion Arm 2B
• Have tumor biopsy-proven CD20+ DLBCL and a clinical history of CLL/SLL.
• Deemed as ineligible for chemoimmunotherapy
• Eligible for treatment with lenalidomide.
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or MRI)
• Must provide a mandatory FFPE tumor tissue sample;
• Females of childbearing potential must use 2 forms of contraception
• A woman of childbearing potential must have a negative serum (beta-hCG) pregnancy test
• Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide
Inclusion Criteria Specific to Subjects With Richter’s Syndrome – R-CHOP Combination Therapy Expansion Arm 2C
• Have tumor biopsy-proven CD20+ DLBCL and have a clinical history of CLL/SLL.
• Eligible to receive R-CHOP per investigator determination.
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or MRI)
• Must provide a mandatory FFPE tumor tissue sample;
Inclusion Criteria Specific to Subjects with R/R CLL – Venetoclax Combination Therapy Dose Escalation Cohorts and Expansion Arm 3
• Must have active CLL/SLL disease that needs treatment
• At least 1 of the following disease-related (constitutional) symptoms:
• Unintentional weight loss = 10% within the previous 6 months
• Significant fatigue
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 46
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125
All Subjects
• Subject received prior treatment with a CD3×CD20 bsAb.
• Subject received any prior allogeneic HSCT or solid organ transplantation
• Subject received treatment with an anticancer agent, as follows:
- Subject received treatment with an investigational drug, within 4 weeks or 5 half lives, whichever is shorter, prior to the first dose of epcoritamab.
• Subject has autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy
• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia (requiring >20 mg of prednisolone daily) or other concurrent uncontrolled medical conditions.
• Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association (see Appendix 3), uncontrolled clinically significant cardiac arrhythmia (CTCAE v5.0 grade 2 or higher), or clinically significant ECG abnormalities
• Myocardial infarction, intracranial bleed, or stroke within the past 6 months
• Subject age =75 and 2 or more active grade =2 cardiovascular conditions.
• Subject has toxicities from previous anticancer therapies that have not resolved to baseline levels or to grade 1 or less except for alopecia and peripheral neuropathy
• Subject has history or presence of clinically relevant disorder affecting the CNS
• ICE score of less than 8 at study entry
• Subject has known past or current malignancy other than inclusion diagnosis, except for:
a.Cervical carcinoma of Stage 1B or less
b.Non-invasive basal cell or squamous cell skin carcinoma
c.Non-invasive, superficial bladder cancer
d.Prostate cancer with a current PSA level <0.1 ng/mL
e.Any curable cancer with a CR of >2 years duration
• Subject has suspected allergies, hypersensitivity, or intolerance to epcoritamab or another anti-CD20 mAb or its excipients (refer to the IB for more information).
• Active HBV (DNA PCR-positive). Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy.
• Active hepatitis C (RNA PCR-positive infection). Subjects who received treatment for HCV that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable
• Subject is a woman who is pregnant or breastfeeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of epcoritamab.
• Subject is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of epcoritamab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method