A Study Evaluating the Prophylactic Use of Tocilizumab to Prevent Cytokine Release Syndrome With Ramantamig Administration in Participants With Relapsed/Refractory Multiple Myeloma

Official title

79635322MMY2002: Phase 2 Randomized, Double-blind, Placebo-controlled Study Evaluating the Prophylactic Use of Tocilizumab to Prevent Cytokine Release Syndrome With Ramantamig Administration in Participants With Relapsed/Refractory Multiple Myeloma

Overview

The purpose of this study is to find out whether giving a single dose of tocilizumab before treatment with ramantamig can help prevent or reduce the severity of cytokine release syndrome (CRS) within 28 days from ramantamig, compared to participants who receive placebo. CRS is an acute inflammatory reaction that can occur during treatment and may be associated with flu-like or other systemic symptoms, such as fever and tiredness.

Interventions

• Drug Ramantamig
  Ramantamig will be administered as subcutaneous (SC) injection.
• Drug Tocilizumab
  Tocilizumab will be administered as intravenous (IV) injection.
• Drug Placebo
  Placebo (saline) will be administered as IV injection.

Primary outcome measures

• Percentage of Participants Alive and Free of Treatment-Emergent American Society for Transplantation and Cellular Therapy (ASTCT) Grade Greater Than or Equal to (>=) 2 Cytokine Release Syndrome (CRS) [Time frame: End of Day 28 from ramantamig dose]

Secondary outcome measures (12)

• Percentage of Participants with Treatment-Emergent CRS of any ASTCT Grade, Grade >=2, and Grade >=3 by the End of Day 28 from Ramantamig Dose [Time frame: End of Day 28 from ramantamig dose]
• Percentage of Participants with Treatment-Emergent CRS of any ASTCT Grade, Grade >=2, and Grade >=3 During Ramantamig Treatment [Time frame: Up to 37 months]
• Percentage of Participants with Re-occurrence of CRS with ASTCT Grade >=2 After the Initial Occurrence of Treatment-Emergent Grade >=2 CRS Event [Time frame: Up to approximately 3 years and 6 months]
• Percentage of Participants with Re-occurrence of CRS for All Grades [Time frame: Up to approximately 3 years and 6 months]
• Overall Response Rate (ORR) [Time frame: Up to approximately 3 years and 6 months]
• Complete Response (CR) or Better [Time frame: Up to approximately 3 years and 6 months]
• Very Good Partial Response (VGPR) or Better [Time frame: Up to approximately 3 years and 6 months]
• Duration of Response (DoR) [Time frame: Up to approximately 3 years and 6 months]
• Time to Response (TTR) [Time frame: Up to approximately 3 years and 6 months]
• Progression-Free Survival (PFS) [Time frame: Up to approximately 3 years and 6 months]
• Time To Next Line of Therapy (TTNT) [Time frame: Up to approximately 3 years and 6 months]
• Time to the First Treatment-emergent Infection with Toxicity Grade >=3 [Time frame: Up to approximately 3 years and 6 months]

Eligibility criteria

Inclusion criteria

• Documented diagnosis of multiple myeloma (MM) as defined by the criteria: a. MM diagnosis according to the international myeloma working group (IMWG) diagnostic criteria; b. Measurable disease at screening as assessed by local laboratory as defined in the protocol
• Received at least 1 prior lines of antimyeloma therapy
• Relapsed or refractory disease as defined: a. Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by the IMWG response criteria greater than (>) 60 days after cessation of treatment.; b. Refractory disease is defined as failure to achieve a response (that is, partial response or better) or confirmed PD by the IMWG response criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment
• Have an eastern cooperative oncology group (ECOG) performance status (PS) score of 0 to 2 at screening and immediately before the start of study treatment administration. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (example, wheelchair-bound due to prior spinal cord injury) and not related to MM or associated therapy
• Have clinical laboratory values meeting the criteria specified in the protocol during the screening and within 1 day of the start of administration of study treatment

Exclusion criteria

• Concurrent use of any other anticancer treatment (including non-palliative radiotherapy) or investigational agent
• Major surgery, (for example, requiring general anesthesia) within 2 weeks before first dose, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
• Suspected or known allergies, hypersensitivity, or intolerance to ramantamig and tocilizumab or their excipients
• Presence of any of the following: a. Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM); b. Any history of malignancy, other than MM, that is considered at high risk of recurrence requiring systemic therapy; c. Any active malignancy other than MM that is considered at high risk of recurrence requiring systemic therapy
• Known active or prior central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Malaysia · 3 centers

• Hospital Ampang — Ampang
• Hospital Sultanah Aminah — Johor Bharu
• Sarawak General Hospital — Kuching

United States · 1 center

• Beverly Hills Cancer Center (BHCC) — Beverly Hills

Identifiers

NCT: NCT07589634 · 79635322MMY2002 · 79635322MMY2002 · 2025-524793-42

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗