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A Phase I Clinical Trial of Y150 in the Treatment of Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05011097
Recruitment Status : Recruiting
First Posted : August 18, 2021
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
Wuhan YZY Biopharma Co., Ltd.

Brief Summary:
The main purpose of this Phase I study is to access the safety and tolerability of Y150 at different dose levels. It is hoped to find out the recommended dose for Phase II/III.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Multiple Myeloma Drug: Y150 Phase 1

Detailed Description:
This is a Phase I, open-label,dose-escalation trial in patients with relapsed or refractory multiple myeloma. There are two parts of the study: a dose-escalation part and a dose-expansion part. Dose escalation follows an accelerated design initially with 2 single subject cohorts (Cohorts 1-2) and switches to a classical 3+3 design (Cohorts 3-7). Dose-expansion means that at least 9 subjects (included subjects of the dose-escalation part) will be selected in 1 - 3 dose levels to focus on the pharmacokinetics (PK) / pharmacodynamic (PD) features and recommended dose for Phase II (RP2D). Additional purpose of the study is to find out whether the study drug has anti-tumor effects.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety, Tolerability, PK/PD and Immunogenicity Characteristics of Recombinant Anti-CD38 and Anti-CD3 Bispecific Antibodies (Y150) for Injection in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : July 8, 2021
Estimated Primary Completion Date : July 30, 2023
Estimated Study Completion Date : December 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Y150
Subjects who meet the enrollment criteria will enter the core treatment period and receive a cycle of treatment with Y150 (once weekly for 4 weeks) via intravenous infusion. And eligible subjects who complete the core treatment period will receive a cycle of extended treatment (once weekly for 4 weeks) until disease progression or toxicity intolerance.
Drug: Y150
Subjects will receive an intravenous infusion of Y150 in a dose escalation once a week for a 28-day treatment cycle until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.




Primary Outcome Measures :
  1. Number of Participants With Adverse Events according to CTCAE V5.0 [ Time Frame: up to approximately 2 years ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  2. Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: From the time of first dosing (Day 1) until the forth dosing (Day 28) ]
    DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0.


Secondary Outcome Measures :
  1. Area under the curve (AUC) of Y150 [ Time Frame: Up to 1 weeks after the fourth dosing. ]
  2. Peak Plasma Concentration (Cmax) of Y150 [ Time Frame: Up to 1 weeks after the fourth dosing. ]
  3. Half-time (t1/2) of Y150 [ Time Frame: Up to 1 weeks after the fourth dosing. ]
  4. lymphocyte subsets in peripheral blood [ Time Frame: 12 months (anticipated) ]
    including CD3/CD4/CD8/CD14/CD19/CD38/CD45/CD56/CD69 lymphocyte subsets in peripheral blood

  5. Cytokines levels in serum [ Time Frame: 12 months (anticipated) ]
    including IL-2, IL-6, IL-8, IL-10, TNF-α, IFN-α, IFN-γ levels in serum

  6. Anti-drug antibodies(ADAs) titer [ Time Frame: 12 months (anticipated) ]
  7. neutralizing antibody titer [ Time Frame: 12 months (anticipated) ]
  8. Objective Response Rate (ORR) [ Time Frame: 12 months (anticipated) ]
    ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR), based on International Myeloma Working Group (IMWG) criteria.

  9. Time to Progression (TTP) [ Time Frame: 12 months (anticipated) ]
    TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression.

  10. Duration of Response [ Time Frame: 12 months (anticipated) ]
    Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.

  11. Progression-Free Survival (PFS) [ Time Frame: 12 months (anticipated) ]
    PFS was defined as the time between the date of first dose of Y150 and either disease progression or death, whichever occurs first.

  12. Overall Survival (OS) [ Time Frame: 12 months (anticipated) ]
    OS was defined as the number of days from administration of the first infusion (Day 1) to date of death.

  13. Time to first Response [ Time Frame: 12 months (anticipated) ]
    Time to first response was defined as the time from the date of first dose of Y150 to the date of initial documentation of a response (PR or better).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 18 years.
  2. Subject has a history of multiple myeloma with relapsed and refractory disease, and must have received at least 2 prior multiple myeloma treatment regimens (including a proteasome inhibitor and an immunomodulatory agent), or can not tolerate the toxicity of PIs and IMIDS; or have drug resistance to one and toxic intolerance to the other.

    1. Relapsed multiple myeloma is defined as IMWG criteria in 2016, including clinical relapse or relapse after CR.
    2. Refractory multiple myeloma is defined as failure of initial or salvage therapy to achieve at least a minimal response (only achieve SD after treatment ≥ 2 cycles ), or disease progression during treatment or within 60 days after the last treatment.
  3. Subjects must have measurable disease, including at least one of the criteria below:

    1. M-protein ≥ 10 g/L by SPEP/immunofixation for subjects with immunoglobulin class G (IgG) myeloma , M-protein ≥ 5g/L for subjects with IgA, IgD, IgE, IgM myeloma or
    2. ≥ 200 mg/24 hours urine collection by UPEP or
    3. Serum free light chain (FLC) levels ≥ 100 mg/L and an abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine M-protein
  4. The interval between the last anti-tumor treatment and the first administration of Y150 (including PIS and IMADs) ≥4 weeks, the interval between CD38 mAb administration and the first administration of Y150 ≥12 weeks;
  5. ECOG performance status 0 - 2;
  6. Life expectancy ≥ 3 months
  7. Adequate hematological function as evidenced by meeting all the following requirements:

    1. Absolute neutrophil count ≥1.0×109/L (growth factor support not allowed within 48h)
    2. Hemoglobin > 70 g/L( without blood transfusion within 7 days)
    3. Platelet count ≥50×109/L(without transfusion within 7 days)
  8. Adequate hepatic function as evidenced by meeting all the following requirements:

    1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST), and alanine aminotransferase (ALT)≤ 2.5 × ULN;
  9. Calculated creatinine clearance (CrCL) ≥ 30 mL/min
  10. Understand and voluntarily sign written informed consent.

Exclusion Criteria:

  1. Subject has central nervous system involvement of multiple myeloma.
  2. Subject has received ≥ 10 mg/day prednisone equivalent within one week before starting Y150.
  3. Subject with primary or secondary plasma cell leukemia.
  4. Subject had a prior autologous stem cell transplant ≤ 12 weeks months prior to starting Y150, or had a prior autologous stem cell transplant history.
  5. Subject received a chimeric antigen receptor T (CAR T) cell product ≤ 6 months prior to starting Y150.
  6. Concurrent malignancy within 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active surveillance, prostate cancer that has undergone definitive treatment, ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma.
  7. Allergy to Abs drugs or human protein.
  8. Active infection(CTCAE Grade ≥2).
  9. Subjects with severe respiratory disease, and to be unsuitable to participate in study by investigators judgment.
  10. Severe cardiovascular disease, including a history of CABG or PCI, myocardial infarction within 6 months of study entry, unstable angina ,NYHA class III or IV heart failure, uncontrolled hypertension or left ventricular ejection fraction <50%
  11. QTc interval > 480 ms; Family or personal with a history of long or short QT syndrome; significant clinical history of ventricular arrhythmias, or currently receiving antiarrhythmic drugs or implanted defibrillator to treat ventricular arrhythmias.
  12. Patients with a history of active autoimmune diseases (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.), except when the disease is in a stable state (without systemic immunosuppressant treatment, the symptoms are stable for more than 6 months).
  13. Patients with severe hyperthyroidism or hypothyroidism.
  14. Patients with metabolic diseases such as uncontrolled diabetes, severe gastrointestinal bleeding, severe diarrhea (Grade ≥ 2 according to CTCAE), or severe gastrointestinal obstruction requiring intervention.
  15. Patients with a history of immunodeficiency, including HIV positive.
  16. HIV antibody, TP antibody and HCV antibody were positive, HBsAg positive and hepatitis B virus DNA test showed that patients with active hepatitis B (HBV-DNA ≥ 1000cps/ml).
  17. Patients who have received inoculation of (attenuated) live virus vaccine within 4 weeks before the first administration.
  18. Pregnant, lactating women, or females or males who have fertility plan within 6 months during the study and after the end of the medication.
  19. Patients with a previous history of definite neurological or psychiatric disorders, and investigator believe that it affects patients' cognitive function or compliance, including unstable epilepsy, dementia, schizophrenia, etc.
  20. Any condition that the investigator believes may not be appropriate for participating the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05011097


Contacts
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Contact: Mengwan Pei 86-27-82668988 peimengwan@yzybio.com

Locations
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China, Tianjin
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Recruiting
Tianjin, Tianjin, China
Contact: Lugui Qiu, MD       qiulg@ihcams.ac.cn   
Principal Investigator: Lugui Qiu, MD         
Principal Investigator: Junyuan Qi, MD         
China, Zhejiang
The First Affiliated Hospital Zhejiang University School of Medicine Not yet recruiting
Hangzhou, Zhejiang, China
Contact: Zhen Cai, MD         
Principal Investigator: Zhen Cai, MD         
Sponsors and Collaborators
Wuhan YZY Biopharma Co., Ltd.
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Responsible Party: Wuhan YZY Biopharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT05011097    
Other Study ID Numbers: Y15001
First Posted: August 18, 2021    Key Record Dates
Last Update Posted: August 18, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases