A Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

November 6, 2024 updated by: He Huang, Zhejiang University

A Pilot Clinical Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

This clinical trial aims to characterize the safety of OL-101 and establish the recommended dose for future research and to evaluate the efficacy of OL-101 (Dose expansion).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will evaluate the safety and efficacy of OL-101, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-Cell Maturation Antigen (BCMA) and G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D). This study is a single-arm, open-label, early exploratory clinical trial, conducted in two phases: dose escalation and dose expansion in adults with multiple myeloma. The trial begins with the dose-escalation phase that focus on safety and tolerability, with interval assessments for potential dose escalation or de-escalation. Recommended dose will be selected at the completion of the dose escalation stage in the dose expansion stage. The study aims to assess safety, pharmacokinetic/pharmacodynamic profiles, and efficacy.

Study Type

Interventional

Enrollment (Estimated)

58

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100071
        • Not yet recruiting
        • Beijing GoBroad Boren Hospital
        • Contact:
        • Contact:
          • Xiequn Chen, MD, PHD
    • Shanxi
      • Xi'an, Shanxi, China, 710016
        • Not yet recruiting
        • The Affiliated Hospital of Northwest University Xi'an No.3 Hospital
        • Contact:
        • Contact:
          • Yajin Zhang, MD, PHD
    • Zhejiang
      • Hangzhou, Zhejiang, China, 3100003
        • Recruiting
        • The First Affiliated Hospital, College of Medicine, Zhejiang University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented diagnosis of multiple myeloma according to the 2014 IMWG diagnostic criteria

  • Relapsed/refractory multiple myeloma as defined by:

    1) Received at least 3 prior lines of MM treatment (must include a PI, an IMiD, and an anti-CD38 antibody).

    2）Disease progression within 12 months of the most recent anti-MM therapy; or disease progression within the past 6 months and subsequently lack response to the most recent line of therapy.

  • Measurable disease at screening as defined by any of the following:

    1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
    2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
  • Positive expression of either BCMA or GPRC5D on bone marrow plasma cells; must be GPRC5D expression positive if previously received BCMA targeted therapy
  • ECOG 0-1
  • Expected life expectancy exceeds 12 weeks

  • Adequate bone marrow reserve or organ function meeting the following criteria:

    1. Hemoglobin ≥ 70 g/L
    2. Platelet count ≥ 50 × 10^9/L
    3. Absolute lymphocyte count ≥ 0.3×10^9/L
    4. Absolute neutrophil count ≥ 1.0 × 10^9/L
    5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN)
    6. Total bilirubin ≤ 2 times ULN; except in subjects with congenital bilirubinemia (such as Gilbert syndrome, in which case the direct bilirubin ≤1.5 × ULN is required)
    7. Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault equation).
    8. corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
    9. SpO2>92% on room air
    10. Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram; no clinically meaningful pericardial effusion by ultrasound

Exclusion Criteria:

  • Solitary plasmacytoma
  • Known active central nervous system (CNS) involvement or exhibits clinical signs of CNS involvement of multiple myeloma.
  • Received allogeneic stem cell transplant; received autologous stem cell transplant within 12 weeks before screening
  • Active second primary malignant tumor, exclude the following: cured non- melanoma skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast
  • Any other significant medical disease, abnormality, or condition that, in the investigator judgment, may make the patient unsuitable for participation in the study or put the patient at risk.
  • Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: OL-101 infusion
This arm provides CAR-T treatment at the dose the patient is assigned to.
Biological: OL-101 infusion
OL-101 infusion will be administered to patients via IV infusion at the assigned dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicity (DLT)
Time Frame: Within 28 days post CAR-T infusion
Adverse events will be assessed based on the CTCAE 5.0
Within 28 days post CAR-T infusion
Treatment emergent adverse event (TEAE) incidence and severity
Time Frame: From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier
Adverse events will be assessed based on the CTCAE 5.0
From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of Immunogenicity
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
To assess the presence of antibodies to OL-101 (ADA)
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Level of RCL
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
To determine whether Replication Competent Lentivirus (RCL) is present in patient that receive OL-101
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Overall response rate (ORR)
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Proportion of subjects with PR or above
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Minimal residual disease (MRD) negative rate
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Proportion of subjects with MRD negative status as defined by the IMWG response criteria
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Duration of response (DOR)
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The time from the initial response to therapy until the disease progression or relapse.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Progression-free survival (PFS)
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The time from CAR-T cell infusion to the first assessment of disease progression or death from any cause.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Overall survival (OS)
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The time from CAR-T cell infusion to death from any cause.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Cmax of OL-101
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The maximum concentration of the CAR-T cells will be measured to assess OL-101 in vivo expansion and persistence.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Tmax of OL-101
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The time of the maximum concentration will be measured to assess OL-101 in vivo expansion and persistence.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
AUC 0-28days of OL-101
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Area under the curve will be measured to assess OL-101 in vivo expansion and persistence.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Serum cytokines
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
The levels of cytokines will be measured, such as IL-6 and ferritin.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Serum soluble circulating BCMA (sBCMA)
Time Frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Serum soluble circulating BCMA will be measured to explore its potential relationship to response or resistance.
Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhejiang University

Collaborators

Overland Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2024

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

September 28, 2024

First Submitted That Met QC Criteria

October 14, 2024

First Posted (Actual)

October 16, 2024

Study Record Updates

Last Update Posted (Estimated)

November 8, 2024

Last Update Submitted That Met QC Criteria

November 6, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OL-101-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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