Clinical Trial To Assess the Efficacy and Safety of PMCC-COE19 in Patients with CD19-Expressing B-Cell Malignancies

Inclusion Criteria49

• Patient (and/or their legal guardian) has provided written informed consent using the PLATYPS Patient Information and Consent Form (PICF)
• Patient must be at least 16 years of age on the day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2
• Have a confirmed diagnosis of a CD19 expressing B-cell malignancy, with confirmed CD19 expression by flow cytometry and/or immunohistochemistry prior to registration. Note: Patients who have had prior treatment with anti CD19 directed cellular or antibody-based therapies will be accepted, so long as detectable CD19 expression on malignant cells can be demonstrated and there is no CD19 meaningful negative population
• Have measurable disease, being either:
• Radiographically assessable nodal and or extra-nodal disease on PET-CT and or MRI brain ± spine, with acceptable recent histological confirmation of
• CD19+ B-cell malignancy, as assessed by the Principal Investigator (PI)
• OR
• Measurable CD19+ B-cell malignancy in peripheral blood and/or bone marrow, which can be quantified in absolute terms (i.e., malignant cells per 109/L) or by percentage of total cells by flow cytometry and/or immunohistochemistry
• Meet at least one of the following disease criteria:
• Have relapsed, or progressed following at least 2 prior lines of systemic therapy, noting that corticosteroids or rituximab monotherapy are not
• considered a line of therapy
• Be refractory to at least one prior line of systemic therapy, noting that corticosteroids or rituximab monotherapy are not considered a line of therapy
• Have relapsed or have had progression of disease within 24 months of initial systemic therapy (POD24), and have no other suitable treatment options in the
• opinion of the Investigator
• Have high grade B-cell lymphoma transformed from a known low-grade lymphoma, with at least 2 prior lines of systemic therapy (including an anthracycline) delivered for the low-grade and high-grade lymphoma combined, noting that corticosteroids or rituximab monotherapy are not considered a line of therapy
• Have relapsed disease after allogeneic or autologous haematopoietic stem cell transplant meeting one of the following:
• o After prior allogeneic transplant, patient has no active graft versus host disease (GVHD [>Grade II]), does not require systemic immunosuppression, is more than 3 months from transplant, and at least 3 months off GVHD prophylaxis
• OR
• o After prior autologous or syngeneic transplant, patient has been more than 3 months from transplant
• Have a life expectancy of greater than or equal to 3 months, as judged by the Investigator
• Adequate haematological function documented within 7 days prior to registration, defined as:
• Haemoglobin greater than or equal to 80 g/L (peripheral red blood cell transfusion support is allowed)
• Absolute neutrophil count (ANC) greater than or equal to 1.0 x 109/L (G-CSF support is allowed, and ANC > 0.5 x 109/L is allowed if neutropenia is due to disease infiltration of bone marrow)
• Absolute lymphocyte count (ALC) greater than or equal to 0.1 x 109/L
• Platelets greater than or equal to 50 x 109/L (platelet transfusion support is allowed for platelets greater than or equal to 30 if due to disease infiltration of bone marrow, or splenomegaly due to disease involvement)
• Adequate cardiac function, defined as:
• Left ventricular ejection fraction (LVEF) greater than or equal to 40% on echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 90 days prior to registration
• No suspicion for intercurrent deterioration in left ventricular function as assessed by the Investigator
• Adequate pulmonary function, defined as:
• Oxygen saturation measured by pulse oximetry greater than or equal to 90% on room air
• Adequate renal function documented within 7 days prior to registration, defined as any one of:
• A serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)
• Creatinine clearance (CrCl) of greater than or equal to 40 mL/min calculated by Cockcroft-Gault formula
• CrCl greater than or equal to 40 mL/min calculated by 24-hour urine collection
• Glomerular filtration rate (GFR) greater than or equal to 40 mL/min by renal scintigraphy
• Adequate hepatic function documented within 7 days prior to registration, defined as all of:
• Total bilirubin less than or equal to 1.5 x ULN (or less than or equal to 3.0 x ULN in patients with Gilbert’s syndrome or documented liver involvement)
• Alanine aminotransferase (ALT) less than or equal to 3.0 x ULN (or less than or equal to 5.0 x ULN in patients with documented liver involvement)
• Aspartate aminotransferase (AST) less than or equal to 3.0 x ULN (or less than or equal to 5.0 x ULN in patients with documented liver involvement)
• Taking a maximum corticosteroid dose of 20 mg of oral prednisolone or equivalent
• Females of childbearing potential (FCBP) and non-sterile male patients (with partners of childbearing potential) must agree to use highly effective methods of contraception from registration on the study to 2 months after the PMCC-COE19 infusion or until PMCC-COE19 is no longer present by quantitative polymerase chain reaction on two consecutive tests whichever is later. Effective methods of contraception are:
• Total abstinence from sexual intercourse when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least 6 weeks prior to registration. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment
• Male sterilisation (at least 6 months prior to Screening), noting that for female patients on the study, the vasectomised male partner should be the sole partner for that patient
• Use of oral, (oestrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months prior to registration
• Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks prior to registration. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential
• Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-hCG) pregnancy test within 3 days prior to registration
• Sexually active male patients must use a condom during intercourse and must agree to refrain from sperm donation, from registration on the study until 52 weeks (12 months) after PMCC-COE19 infusion