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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05801939




Registration number
NCT05801939
Ethics application status
Date submitted
24/03/2023
Date registered
6/04/2023
Date last updated
1/10/2024

Titles & IDs
Public title
Cevostamab Following CAR T Cell Therapy for RRMM
Scientific title
Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy for Relapsed/Refractory Multiple Myeloma
Secondary ID [1] 0 0
853124, UPCC 02423
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cevostamab

Experimental: Cevostamab -


Treatment: Drugs: Cevostamab
Cevostamab will be given as an IV infusion once every 3 weeks, starting roughly 10 weeks (day 70 +/- 4 days) post-CAR T cell infusion, with subjects planned to receive 8 cycles initially. Subjects receive a single step-up dose of 3.6 mg of cevostamab on cycle 1, day 1 (C1D1), followed by the recommended target dose (160 mg, 132mg, or 90 mg based on results of safety run-in data and safety review) on C1D8. Myeloma responses are assessed every cycle, and a repeat bone marrow aspirate and biopsy (BMbx) is performed at the start of cycle 8. If participants are not in an MRD-negative CR at this timepoint (or if the BM bx is inevaluable/indeterminate for CR or MRD testing), they continue with another 8 cycles (C9-16) of cevostamab. If they are in MRD-negative CR at start of C8, they stop therapy after receiving this cycle and are observed.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MRD-negative complete remission (CR)
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Safety and tolerability (Incidence of Treatment-Emergent Adverse Events) of cevostamab administration post-BCMA CAR T cell therapy
Timepoint [1] 0 0
infusion start Day 56 through 30 days post final infusion
Secondary outcome [2] 0 0
Feasibility of cevostamab administration post-BCMA CAR T cell therapy
Timepoint [2] 0 0
Day 56 and completion through day 203
Secondary outcome [3] 0 0
Impact of cevostamab consolidation post-BCMA CAR T cell therapy on other clinical outcomes
Timepoint [3] 0 0
6 and 12 months post-CAR T cell therapy

Eligibility
Key inclusion criteria
1. Signed Informed Consent Form(s)
2. Age =18 years at time of signing Informed Consent Form
3. Ability to comply with the study protocol
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. Life expectancy of at least 12 weeks
6. Participants must have relapsed and/or refractory multiple myeloma with therapy that must include a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38 antibody, and have received a BCMA-directed CAR T cell product as standard of care (i.e. not on a clinical trial) as per the current FDA label, between 6 and 10 weeks prior to enrollment, and have not had progressive disease by IMWG criteria since CAR T cell infusion. Patients who have received out-of-specification CAR T cell products are not eligible.

1. For patients who received ide-cel, they must have had at least 2 prior lines of therapy prior to ide-cel
2. For patients who received cilta-cel, they must have had at least 2 prior lines prior to cilta-cel, or 1 prior line and be refractory or intolerant to lenalidomide.
7. Agreement to provide bone marrow biopsy and aspirate samples
8. Non-hematologic adverse events from prior anti-cancer therapy resolved to Grade = 1, with the certain exceptions.
9. Measurable disease is not required for study entry
10. Laboratory values as follows:

a. Hepatic function i. AST and ALT = 3 x ULN ii. Total bilirubin = 1.5 x ULN; b. Hematologic function (cevostamab criteria should be met both at screening (to determine eligibility), as well as on Cycle1, Day 1) i. Platelet count = 50,000/mm3 without transfusion within 7 days prior to first dose ii. ANC = 1000/mm3 iii. Total hemoglobin = 7 g/dL c. Creatinine clearance (CrCl) = 30 mL/min d. Serum calcium (corrected for albumin) level at or below Grade 1 hypercalcemia
11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, as defined in the protocol.
12. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined in the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to comply with protocol-mandated hospitalization and activities restrictions
2. Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose of study drug

a. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
3. Participants who had = Grade 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) by ASTCT criteria, or any grade macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH)after CAR-T therapy are excluded
4. Participants who had any grade movement and/or neurocognitive disorder attributed to CAR T cells are excluded.
5. Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first cevostamab infusion
6. Known treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents as in the protocol.
7. Treatment with any chemotherapeutic agent, or any other anti-cancer agent (investigational or otherwise) during the time period between CAR T cell infusion and first cevostamab infusion, with the following exceptions:

1. Therapies used for treatment of CAR T cell-related toxicities (e.g. steroids, cyclophosphamide) will not be a cause for exclusion, as long as washout period listed below (2 weeks) is met
2. Short course palliative radiation post-CAR T cell therapy (e.g. for severe bone pain, impending fracture) is allowed as long as completed at least 1 week prior to first dose of cevostamab.
8. Received systemic immunosuppressive medications (including, but not limited to, steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tocilizumab, siltuximab, anakinra, ruxolitinib, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment = 10 mg/day prednisone or equivalent, within 2 weeks prior to first dose of cevostamab

a. Participants who received acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea) may be enrolled in the study.

i. The use of inhaled corticosteroids is permitted. ii. The use of mineralocorticoids for management of orthostatic hypotension is permitted.

iii. The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
9. Autologous stem cell transplantation (SCT) within 100 days prior to first cevostamab infusion
10. Prior allogeneic SCT within 12 months prior to first cevostamab infusion. Participants with prior allogeneic SCT must have no evidence for active graft-versus-host-disease (GVHD) and be off all therapy for GVHD for at least 3 months prior to first cevostamab infusion.
11. Prior solid organ transplantation
12. History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

1. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
2. Participants with history of immune thromobocytopenic purpura (ITP), autoimmune hemolytic anemia, or other immune-mediated conditions that solely affect blood counts, as long as these conditions are not active at the time of enrollment and subjects otherwise meet hematologic parameters for eligibility, may be eligible with approval from Sponsor Medical Director.
13. Participants with history of confirmed progressive multifocal leukoencephalopathy
14. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
15. History of other malignancy that could affect compliance with the protocol or interpretation of results

1. Participants with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed.
2. Participants with a malignancy that has been treated with curative intent will also be allowed if the malignancy has been in remission prior to first cevostamab infusion.
16. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM

1. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator are allowed.
2. Participants with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications are allowed.
17. Significant cardiovascular disease (such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, uncontrolled arrhythmias, or unstable angina) that may limit a subject's ability to adequately tolerate a cytokine release syndrome (CRS) event
18. Symptomatic active pulmonary disease or requiring supplemental oxygen
19. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics within 14 days prior to first cevostamab infusion. Empiric or prophylactic antibiotics administered during neutropenia or neutropenic fever without microbiologic evidence of infection do not exclude subjects.

a. Participants with asymptomatic CMV reactivation (i.e. positive CMV PCR) found at screening may enroll after discussion with the Medical Director.
20. Known or suspected chronic active Epstein-Barr virus (EBV) infection. Guidelines for diagnosing chronic active EBV infection are provided by Okano et al. (2005).
21. Recent major surgery within 4 weeks prior to first cevostamab infusion

a. Protocol-mandated procedures (e.g., bone marrow biopsies) are permitted.
22. Positive serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection

a. Participants whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation.
23. Acute or chronic hepatitis C virus (HCV) infection

a. Participants who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation.
24. Known history of HIV seropositivity
25. Administration of a live, attenuated vaccine within 4 weeks before first cevostamab infusion or anticipation that such a live attenuated vaccine will be required during the study

1. Influenza vaccination should be given during influenza season (approximately October to May in the Northern Hemisphere). Subjects must not receive live, attenuated influenza vaccine (e.g., FluMist®) at any time during the study treatment period.
2. SARS-CoV-2 vaccines may be given in accordance with the approved/authorized vaccine label and official/local immunization guidance. SARS-CoV-2 vaccines must not be administered within 1 week before first study treatment or during Cycle 1.
3. Investigators should review the vaccination status of potential study subjects being considered for this study and follow the U.S. Centers for Disease Control and Prevention guidelines for adult vaccination with any other non-live vaccines intended to prevent infectious diseases prior to study.
26. Any medical condition or abnormality in clinical laboratory tests that, in the Medical Director's judgment, precludes the subject's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2028
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania

Funding & Sponsors
Primary sponsor type
Other
Name
University of Pennsylvania
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 2, open-label, single-arm, single stage, single-institution study, with an initial safety run-in period. Potential participants with relapsed/refractory myeloma who are undergoing standard of care, commercially-available BCMA-directed CAR T cell therapy may be identified pre-CAR T cell infusion but are not consented and enrolled until at least 4-6 weeks after CAR T cell infusion, once recovered from acute toxicities. Note: the lymphodepleting chemotherapy and CAR T cell therapy is being administered as part of standard clinical practice and is not considered part of this protocol. Alternative lymphodepleting regimens other than fludarabine and cyclophosphamide (eg in the setting of fludarabine shortages) are acceptable. Cevostamab will be given as an IV infusion once every 3 weeks, starting roughly 10 weeks (day 70 +/- 4 days) post-CAR T cell infusion, with subjects planned to receive 8 cycles initially. Aiming to assess the impact of cevostamab consolidation post-BCMA CAR T cell therapy on rate of MRD-negative complete remission (CR) at 12 months.
Trial website
https://clinicaltrials.gov/study/NCT05801939
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Adam D Cohen, MD
Address 0 0
University of Pennsylvania
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sara Whittington
Address 0 0
Country 0 0
Phone 0 0
215-220-9688
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05801939