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

Multiple Myeloma Clinical Trial

— iMMagine-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05396885
• Other study ID #: ARC-112A
• Status: Recruiting
• Phase: Phase 2
• Start date: August 9, 2022
• Est. completion date: May 31, 2025

Study information

• Verified date: April 2024
• Source: Gilead Sciences
• Contact: Clinical Information
• Phone: 240-327-0379
• Email: clinical[@]arcellx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a Phase II open-label study of anitocabtagene-autoleucel * in patients with relapsed or refractory multiple myeloma (MM). The study will have the following sequential phases: screening, enrollment, pre-treatment with lymphodepleting chemotherapy, treatment with anitocabtagene-autoleucel , and follow-up. If necessary, bridging therapy is allowed to control growth of MM disease while anitocabtagene-autoleucel is being manufactured.

Following a single infusion of anitocabtagene-autoleucel both safety and efficacy data will be assessed. Efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years, or upon patient relapse. The primary analysis will be conducted approximately 13 months after the final patient is dosed. This will allow approximately 12 months follow up from the time of the last observed response on study.

Long-term safety data will be collected under a separate long-term follow up study for up to 15 years per health authority guidelines.

*Anitocabtagene-autoleucel drug product consists of autologous T cells that have been genetically modified ex vivo to express a D-domain Chimeric Antigen Receptor (CAR), followed by a cluster of differentiation 8 (CD8) hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB and CD3ξ, that specifically recognizes B-cell maturation antigen (BCMA). The active substance of anitocabtagene-autoleucel is CAR+ CD3+ T cells that have undergone ex vivo T-cell activation, gene transfer by replication-deficient lentiviral vector, and expansion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ?/? 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• anitocabtagene-autoleucel
Anitocabtagene-autoleucel-directed CAR T-cell therapy using a novel, synthetic binding domain, called a D-domain

Locations

Country	Name	City	State
United States	Northside Hospital, Inc	Atlanta	Georgia
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Maryland School of Medicine Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Levine Cancer Institute at Atrium Health	Charlotte	North Carolina
United States	The University of Chicago Biological Sciences	Chicago	Illinois
United States	Simmons Comprehensive Cancer Center at UT Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Hospital	Detroit	Michigan
United States	John Theurer Cancer Center at Hackensack Meridian Health	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	UW Carbone Cancer Center	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oregon Health & Sciences University - Knight Cancer Institute	Portland	Oregon
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Honor Health	Scottsdale	Arizona
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Kite, A Gilead Company	Arcellx, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	ORR Per International Myeloma Working Group (IMWG) criteria, as assessed by an independent review committee (IRC)	24 Months
Secondary	Stringent complete response (sCR) or complete response (CR) rate	The proportion of subjects in whom best response of sCR or CR,as assessed by an independent review committee (IRC) per by IMWG criteria	24 Months
Secondary	Overall Response Rate (ORR) of subjects limited to three lines of prior treatment	ORR per IMWG criteria, as assessed by an independent review committee (IRC), of subjects limited to three lines of prior treatment	24 Months
Secondary	Duration of Response (DoR)	Time from the date of first documentation of response of PR or better per IMWG criteria after anitocabtagene-autoleucel infusion to the earlier of first documentation of disease progression per IMWG criteria or death	24 Months
Secondary	Very Good Partial Response (VGPR) Rate and Partial Response (PR) Rate	The proportion of subjects with best response of VGPR and PR, respectively, by IMWG criteria	24 Months
Secondary	Time to Initial Response	Time to initial response measurement of time from the date of infusion of anitocabtagene-autoleucel to the date upon which the first IMWG response (i.e., PR or better) occurs	24 months
Secondary	Progression Free Survival (PFS)	Measurement of time from the date of infusion of anitocabtagene-autoleucel to the date upon which the IMWG criteria for progressive disease or death occurs	24 Months
Secondary	Overall Survival (OS)	Measurement of time (e.g., days or months) from the date of infusion of anitocabtagene-autoleucel to the date upon which death from any cause occurs	24 Months
Secondary	Safety Profile of anitocabtagene-autoleucel as assessed by incidence and severity of adverse events	Summarization of adverse event (AE) terms, frequency, and severity using CTCAE version 5.0, the adverse events of special interest (AESIs), the serious adverse events (SAEs)	24 Months
Secondary	Pharmacokinetics of anitocabtagene-autoleucel	Define the Pharmacokinetics of anitocabtagene-autoleucel using vector copy number (VCN) on peripheral mononuclear cells at defined timepoints. Quantification of anitocabtagene-autoleucel cells using vector copy number (VCN) on peripheral blood mononuclear cells	24 Months
Secondary	Anti-anitocabtagene-autoleucel Antibodies	Proportion of subjects who develop antibodies against anitocabtagene-autoleucel and the timing and titer of antibodies developed	24 Months
Secondary	Health Related Quality of Life (HRQoL)	Measure the change in HRQoL pre- versus post-treatment with anitocabtagene-autoleucel	24 Months
Secondary	Minimal Residual Disease (MRD) negativity	The proportion of subjects that are MRD negative (i.e., no measurable tumor cells in at least 105 cells isolated from the bone marrow) from the EE population and from the MRD evaluable population (i.e., those subjects with baseline sample allowing MRD calibration)	24 Months
Secondary	Time to Progression (TTP)	Measurement of time from date of anitocabtagene-autoleucel infusion to first documented IRC assessed progression using IMWG criteria or death due to disease progression	24 Months