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

Cancer Categories

Hematologic (Blood Cancers)

Karmanos Trial ID

2022-078

NCT ID

NCT05396885

Age Group

Adult

Scope

National

Phase

Phase II

Principal Investigator

Abhinav
Deol, M.D.
Oncology - Hematology, Oncology - Medical View Profile

Objective:

Primary Objectives:

TThe 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 Objectives:

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 further characterize the safety of CART-ddBCMA in subjects with RRMM
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 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 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.

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Eligibility

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 (IMiD) 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.

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; filgrastim (or biosimilar) not allowed within 7 days, pegfilgrastim (or biosimilar) within 14 days]

Creatinine clearance ≥45 mL/min min (as determined by the Cockgroft-Gault equation) 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 (Subjects with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within one year 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. NOTE: Leukapheresis will be performed only after all other eligibility criteria are confirmed

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
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

Subjects with solitary plasmacytomas without evidence of other measurable disease are excluded
History of allergy or hypersensitivity to study drug components. Subjects with a history of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO) are excluded
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 (i.e., New York Heart Association stage III or IV)
Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to Screening
Significant pulmonary dysfunction
Uncontrolled thromboembolic events or recent severe hemorrhage (i.e., within one year)
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, and 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 are eligible

Active central nervous system (CNS) involvement by malignancy
Any sign of active or prior CNS pathology including but not limited to 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.
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
Any vaccine ≤ 6 weeks before leukapheresis and/or anticipation of the need for such a vaccine during the subject's participation in the study
Concurrent enrollment on another study using an investigational therapy for the treatment of RRMM

Locations

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Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

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Farmington Hills, MI 48334
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Phone: 800-527-6266

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