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

Protocol # :
Multiple Myeloma
Disease Sites
Multiple Myeloma
Principal Investigator
Frigault, Matt, J
Site Research Nurses
Gammon, Marilyn
Noyes, Sarah, M.
Weigel, Susan

Trial Description

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

Eligibility Requirements

Inclusion Criteria:

1. Age 18 years or older and has capacity to give informed consent

2. 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

3. Documented measurable disease including at least one or more of the following

1. Serum M-protein ≥1.0 g/dL

2. Urine M-protein ≥200 mg/24 hours

3. Involved serum free light chain ≥10 mg/dL with abnormal κ/λ ratio (i.e., >4:1
or <1:2)

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5. Life expectancy >12 weeks

6. Adequate organ function defined as:

1. Oxygen (O2) saturation ≥92% on room air

2. Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiogram (ECHO) or
multigated acquisition (MUGA) scan

3. 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

4. Creatinine clearance ≥45 mL/min min (as determined by the Cockgroft-Gault
equation) and not on dialysis

5. Aspartate transaminase (AST)/alanine transaminase (ALT) <3 x upper limits of
normal (ULN)

6. Total bilirubin <1.5 x ULN (allow 3x ULN for Gilbert's syndrome)

7. 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)

7. 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

8. 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

9. 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

10. 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:

1. Plasma cell leukemia or history of plasma cell leukemia

2. Treatment with the following therapies as specified below

1. Any prior systemic treatment for multiple myeloma within the 14 days prior to
scheduled leukapheresis

2. 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

3. Prior treatment with any gene therapy or gene-modified cellular immune-therapy

4. Prior B-cell maturation antigen (BCMA) directed therapy

5. Autologous stem cell transplantation within 3 months prior to leukapheresis, or
any prior allogeneic stem cell transplantation

3. Subjects with solitary plasmacytomas without evidence of other measurable disease
are excluded

4. History of allergy or hypersensitivity to study drug components. Subjects with a
history of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO) are

5. Contraindication to fludarabine or cyclophosphamide

6. Severe or uncontrolled intercurrent illness or laboratory abnormalities including

1. 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)

2. Symptomatic congestive heart failure (i.e., New York Heart Association stage
III or IV)

3. Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months
prior to Screening

4. Significant pulmonary dysfunction

5. Uncontrolled thromboembolic events or recent severe hemorrhage (i.e., within
one year)

6. 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.

7. Auto-immune disease requiring immunosuppressive therapy within the last 24

7. Seropositive for and with evidence of active hepatitis B or C infection at time of
Screening, or HIV seropositive

1. Subjects with a history of hepatitis B but have received antiviral therapy and
have non-detectable viral DNA are eligible

2. Subjects seropositive because of hepatitis B virus vaccine with no signs or
active infection are eligible

3. Subjects who had hepatitis C but have received antiviral therapy and show no
detectable hepatitis C virus (HCV) viral RNA are eligible

8. Active central nervous system (CNS) involvement by malignancy

9. 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

10. 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.

11. Females who are pregnant or breastfeeding or females of childbearing potential not
using an effective method of birth control

12. 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

13. Any vaccine ≤ 6 weeks before leukapheresis and/or anticipation of the need for such
a vaccine during the subject's participation in the study

14. Concurrent enrollment on another study using an investigational therapy for the
treatment of RRMM