HealthTree Myeloma Clinical Trials Study of CART-ddBMCA in Relapsed or Refractory Multiple Myeloma (iMMagine-1)

Clinical Trial

Recruiting

Study of CART-ddBMCA in Relapsed or Refractory Multiple Myeloma (iMMagine-1)

          A Phase II study of CART-ddBCMA for patients with relapsed or refractory multiple myeloma. CART-ddBCMA is a BCMA-directed CAR-T cell therapy

Est. Enrollment: 110 participants

Study Start Date: Aug 09, 2022

Study Completion Date: May 31, 2025

Age: 18+ years

Gender: All

Who can join

Age 18 years or older and has capacity to give informed consent
Relapsed or refractory multiple myeloma treated with at least 3 prior regimens of systemic therapy including proteasome inhibitor, immunomodulatory drugs (IMiDs) and anti-CD38 antibody and are refractory to the last line of therapy. For each line, 2 consecutive cycles are required unless the best response after 1 cycle was progressive disease.
a. Note: IMWG criteria defines refractory disease as disease progression on or within 60 days of a therapy Note: Induction treatment with or without hematopoietic stem cell transplant and with or without maintenance is considered a single regimen
Documented measurable disease including at least one or more of the following criteria:
Serum M-protein ≥1.0 g/dL
Urine M-protein ≥200 mg/24 hours
Involved serum free light chain ≥10 mg/dL with abnormal κ/λ ratio (i.e., >4:1 or <1:2)
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Life expectancy >12 weeks
Adequate organ function defined as:
Oxygen (O2) saturation ≥92% on room air
Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
Absolute neutrophil count (ANC) ≥1.0k/µl, platelet count (PLT) ≥50k/µl, (NOTE: Platelet transfusion not allowed within 14 days; growth factor neupogen not allowed within 7 days, neulasta within 14 days)
Creatinine clearance ≥30 mL/min and not on dialysis
Aspartate transaminase (AST)/alanine transaminase (ALT) <3 x upper limits of normal (ULN)
Total bilirubin <1.5 x ULN (allow 3x ULN for Gilbert's syndrome)
Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio (INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Patients with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within 60 days are excluded)
Resolution of adverse events (AEs) from any prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensory neuropathy)
Male and female participants of childbearing potential must agree to use highly effective methods of birth control through 12 months after the dose of study treatment
Willing to comply with and able to tolerate study procedures, including consent to participate in separate Long-term Safety Follow-up lasting up to 15 years per FDA guidance
Subject's leukapheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site

Who cannot join

Plasma cell leukemia or history of plasma cell leukemia
Treatment with the following therapies as specified below
Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis unless discussed with medical monitor
Receiving high-dose (e.g., >10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis
Prior treatment with any gene therapy or gene-modified cellular immune-therapy
Prior B-cell maturation antigen (BCMA) directed therapy
Autologous stem cell transplantation within 3 months prior to leukapheresis, or any prior allogeneic stem cell transplantation
Patients with solitary plasmacytomas without evidence of other measurable disease
History of allergy or hypersensitivity to study drug components. Patients with a history of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO)
Contraindication to fludarabine or cyclophosphamide
Severe or uncontrolled intercurrent illness or laboratory abnormalities including
Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, (e.g., related to disease)
Symptomatic congestive heart failure
Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to Screening
Significant pulmonary dysfunction
Uncontrolled thromboembolic events or recent severe hemorrhage
Any history of pulmonary embolism (PE) in the past 12 months or deep vein thrombosis (DVT) within three months of enrollment. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of PE/DVT if greater than twelve and three months, respectively, from time of enrollment, should be at a stable maintenance dose.
Auto-immune disease requiring immunosuppressive therapy
Seropositive for and with evidence of active hepatitis B or C infection at time of Screening, or HIV seropositive
Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible
Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible
Active central nervous system (CNS) involvement by malignancy. NOTE: subjects who are asymptomatic, stable, and received prior effective treatment for CNS disease may be eligible after discussion with medical monitor
Any sign of active or prior CNS pathology including history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis
Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the medical monitor
Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control
Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk