Extramedullary Myeloma
Conditions
Brief summary
This clinical trial will investigate the in vivo trafficking of cilta-cel in extramedullary myeloma using 64Cu Super Paramagnetic Iron Oxide Nanoparticle (64Cu SPION) and Positron Emission Tomography-Magnetic Resonance Imaging (PET-MRI)
Detailed description
This a Phase Ib exploratory study designed to investigate the in vivo trafficking of cilta-cel in extramedullary myeloma (EMM) using 64Cu SPION nanoparticles and PET-MRI imaging. It is planned that 10-30% of clinical dose of target number of cilta-cel will be labelled. The target number cilta-cel has been chosen based on the previous first in humans (FIH) study. The rationale to label of cilta-cel in the range of ≤30% is to ensure that reasonable positron emission tomography (PET) and magnetic resonance (MR) imaging quality by increasing the relative labelling dose, in the case low cell numbers are obtained. Additionally, the selected range is chosen to limit cellular toxicity and radiation exposure to the patient from the labelled cells. The unlabeled and labelled dose will be administered as scheduled by a two-part intravenous infusion in which the labelled cells are administered no later than 4hrs after the unlabeled infusion
Interventions
BIOLOGICALCombination Product: JNJ-68284528 (Cilta-cel) & 64Cu SPION dual PET-MR imaging agent
Cilta-cel is a cellular immunotherapy derived from autologous CD3+ T-cells that have undergone ex vivo modification to target B-Cell Maturation Antigen (BCMA) on the surface of plasma cells. Cilta-cel will be administered as two IV infusions, ≥70% unlabeled and ≤30% labelled. The dose will be based on the patient's weight (kg) at apheresis
Sponsors
Peter MacCallum Cancer Centre, Australia
Janssen, LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet all the following criteria for study entry: 1. Patient has provided written informed consent 2. Patient is \>18 years of age at the time of consent 3. Patient has a documented diagnosis of MM according to the IMWG diagnostic criteria (Appendix 1) 4. Measurable extramedullary disease by any imaging modality (at least one site of disease ≥1cm that has never received radiotherapy or has progressed following radiotherapy). Presence of biochemical measurable disease is not required 5. Have received at least 2 prior lines of therapy including a PTI and an IMiD. Patient must have undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy (Appendix 2) Note: induction with or without haematopoietic stem cell transplant, consolidation and maintenance therapy is considered a single line of therapy. 6. Have an ECOG Performance Status score of 0 or 1 (Appendix 3) 7. Have a life expectancy of ≥3 months, as judged by the Investigator 8. Able to undergo apheresis for mononuclear cell collection 9. Have clinical laboratory values meeting the following criteria within 7 days prior to registration (enrolment): * Haemoglobin ≥80g/L (recombinant human erythropoietin use is permitted) * ANC ≥1 × 109/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) * Platelet count ≥50 × 109/L * Absolute lymphocyte count ≥0.3 × 109/L * AST ≤3.0× ULN * ALT ≤3.0× ULN * Total bilirubin ≤2.0× ULN; except in patients with congenital bilirubinaemia, such as Gilbert's syndrome (in which case direct bilirubin ≤2.0× ULN is required) * Calculated CrCl ≥40mL/min calculated by the Cockcroft-Gault formula (Appendix 4), nuclear medicine assessment or a 24-hour urine collection 10. When a woman is of childbearing potential, the patient must commit either to abstaining continuously from heterosexual intercourse or agree to practice 2 methods of reliable birth control simultaneously. Where one of the methods is highly effective method of contraception (failure rate of \<1% per year when used consistently and correctly; see examples below) and one other effective method (i.e., male latex or synthetic condom, diaphragm, or cervical cap) and patient must agree to remain on both methods from the time of signing the PICF until at least 1 year after receiving a cilta-cel infusion (Appendix 5). Reliable contraception is indicated even where there has been a history of infertility, unless it is due to hysterectomy. WOCBP should be referred to a qualified provider of contraceptive methods, if needed. Examples of highly effective contraceptives include: * User-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone-releasing system; 3) vasectomised partner * User-dependent method: progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable) 11. A man must commit either to abstaining continuously from heterosexual intercourse or a man who is sexually active with a WOCBP or a pregnant woman must agree to use a barrier method of contraception (e.g., latex or synthetic condom with spermicidal foam/gel/film/cream/suppository) from the time of signing the PICF until at least 1 year after receiving a cilta-cel, even if they have undergone a successful vasectomy 12. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a cilta-cel infusion 13. Patient must be willing and able to adhere to the following lifestyle restrictions during the study to be eligible for participation: * Refer to Section 8.6.3, Prohibited Therapies for details regarding prohibited and restricted therapy during the study * Agree to follow all requirements that must be met during the study as noted in the Inclusion and
Exclusion criteria
(e.g., contraceptive requirements)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the utility of 64Cu SPION labelling for in vivo real time monitoring of trafficking of anti-BCMA Chimeric Antigen Receptor T-Cell (CAR-T) cells in Relapsed/ Refractory (RR) EMM. | assessed up to one month (first month after infusion) | Detectable cells by PET assessed by the Deauville score \>3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of 64Cu SPION labelled cilta-cel for EMM | From date of signing consent until study completion, assessed up to approximately 31 months | Incidence, nature and severity of adverse events (AEs) according to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) and 2019 American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria for cytokine release syndrome (CRS) and neurotoxicity, Serious Adverse Events (SAE), and Adverse Events of special interest (AESI) |
| Complete response rate (CRR) by International Myeloma Working Group (IMWG) criteria | assessed up to approximately 13 months | Using IMWG criteria |
| Overall response rate (ORR) by IMWG criteria | assessed up to approximately 13 months | Using IMWG criteria |
| Minimal residual disease response by Adaptive ClonoSeq assay | assessed up to approximately 13 months | on ctDNA at Day +1, Day +28, 12 weeks, 24 weeks, and 52 weeks post Day +28 and on Bone Marrow Aspirate (BMA) at Day +28 and at suspected CR |
| Duration of Response by IMWG criteria | assessed up to approximately 13 months | Defined as time from first response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR) to time to progressive disease (PD) |
| Progression free survival, defined as time from study enrolment until biochemical, radiological and/or clinical PD or death, according to IMWG criteria | assessed up to approximately 13 months | by IMWG criteria |
| Overall survival (OR) | assessed up to approximately 31 months | defined as time from study enrolment to death |
Countries
Australia
Contacts
PRINCIPAL_INVESTIGATORSimon Harrison
Peter MacCallum Cancer Centre, Australia
Outcome results
None listed