Clinical Trial 22086

• Overview

  Study Title:

  A Phase II Study of CART-ddBCMA for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

  Summary:

  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

  Objective:

  Primary The primary objective of this study is to determine the efficacy, as assessed by ORR, of CARTddBCMA in subjects with relapsed or refractory multiple myeloma (RRMM). Secondary -To further characterize the safety of CART-ddBCMA in subjects with RRMM -To determine the efficacy, as assessed by ORR, of CART-ddBCMA in subjects with relapsed or refractory multiple myeloma (RRMM) limited to three lines of prior treatment -To describe depth (i.e., rate of CR/sCR, VGPR, PR) and duration of responses (DoR), progression free survival (PFS), Time to Progression (TTP), and Overall Survival (OS) -To characterize the cell expansion kinetics of CART-ddBCMA in terms of peak quantification in peripheral blood, timing of peak expansion, relationship of peak expansion timing and quantification to efficacy and toxicity as assessed by vector copy number (VCN) -To characterize cell persistence of CART-ddBCMA and relationship to efficacy as assessed by vector copy number (VCN) measurability at each timepoint -To characterize the anti-CART-ddBCMA antibody response in subjects with RRMM -To characterize the impact of CART-ddBCMA in subjects with RRMM on healthrelated quality of life (HRQoL) using the EQ-5D-5L, EORTC-QLQ-C30, and EORTCQLQ- My20 quality of life assessments. Exploratory -To characterize the impact of baseline tumor burden in patients with RRMM on efficacy, safety, and cell expansion -To characterize the frequency with which minimal residual disease (MRD) becomes undetectable (i.e., MRD-negative) in subjects with RRMM after treatment with CARTddBCMA and assess the relationship of MRD-negativity to ORR, CR/sCR rate, DoR, PFS, TTP, and OS -To characterize serum cytokine levels during the screening and treatment periods and any relationship to efficacy and/or safety -To characterize the phenotype of CART-ddBCMA cells in the peripheral blood and bone marrow, when possible, using flow cytometry -To characterize the quantity of soluble BCMA (sBCMA) in subjects with RRMM treated with CART-ddBCMA and the relationship of sBCMA to efficacy and safety -To characterize drug product attributes and their relationship to efficacy and/or safety -To determine and understand the manufacturing outcomes and drug product related attributes -To measure healthcare resource utilization

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  CART-ddBCMA (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  • 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.
  • Documented measurable disease
  • ECOG performance status 0-1
  • Life expectancy >12 weeks
  • Adequate organ function defined by protocol
  • 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

• Exclusion Criteria

  • 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 (i.e., within one year) 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 within the last 24 months. 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 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.
  • 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

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