Study Details

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Multiple Myeloma

Gender

N/A

Date

August 2022 - December 2026

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

anitocabtagene-autoleucel

Eligibility Information

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 criteria:
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 days]
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 neuropathy)
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 treatment
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 guidance
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 leukapheresis
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 excluded
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 months
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

Locations

Locations (18)

HonorHealth Cancer Transplant Institute

Scottsdale, Arizona, United States, 85258

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Northside Hospital

Atlanta, Georgia, United States, 30342

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

Oregon Health & Science University (OHSU)

Portland, Oregon, United States, 97239

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States, 84112

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States, 53792

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Study of Anitocabtagene-autoleucel in Relapsed or Refractory Multiple Myeloma (iMMagine-1) (iMMagine-1)

OVERVIEW

PROTOCOL SUMMARY