B001 in Patients With CD20 Positive B-cell Non Hodgkin's Lymphoma

Phase Ia Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Recombinant Humanized Anti-CD20 Monoclonal Antibody for Injection(B001)

It's the first-in-human study of Recombinant Humanized Anti-CD20 Monoclonal Antibody for Injection (B001). The main purpose of this study is to explore the safety and tolerance of B001 for patients with CD20 positive B-cell non Hodgkin's lymphoma. It will also explore the PK/PD manner and ORR in this study.

Study Overview

• Status: Completed
• Conditions: CD20 Positive B Cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Biological: B001

Detailed Description

Phase I dose escalation study

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • The second Affiliated Hospital of Guangzhou Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age of 18-75, male or female.
2. Patients with the following histologically-documented hematologic malignancy: CD20 positive B-cell non Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to 2016 WHO Classification of Lymphoma.
3. Patients with relapsed/refractory CD20 positive B cell NHL (including CLL/SLL )
4. Life expectancy of at least 6 months.
5. ECOG-PS score of 0-1.
6. For patients of reproductive potential, pregnancy test should be negative 7 days before treatment , and use of a reliable means of contraception during the study and 12months after discontinuing treatment. Males should be willing to use barrier contraception during the study and 12months after discontinuing treatment.
7. Provision of signed and dated ,written informed consent prior to any study specific procedures, sampling and analyses.

Exclusion Criteria:

1. Serious blood, renal or hepatic function impairment:

   • Absolute neutrophil count(ANC)<1.0*10^9/L（Except for those with bone marrow invasion）
   • Lymphocyte Count(LYM)>50*10^9/L
   • Haemoglobin(Hb)<70g/L（Except for those with bone marrow invasion）
   • Platelet count(PLT)<50*10^9/L（Except for those with bone marrow invasion）
   • Creatinine (Cr)>1.5xULN
   • Alanine transaminase (ALT)or Aspartate aminotransferase(AST)>2.5xULN
   • Total bilirubin (TBIL)>2xULN
2. Patients with any anti-tumor treatment (including steroid treatment) within 4 weeks or with any chronic unresolved toxicities from prior therapy greater than Grade 2 according to NCI-CTCAE 4.03.
3. Rituximab or any other anti-CD20 monoclonal antibody treatment within 3 weeks.
4. received blood transfusion and hemopoietic stimulating factor,eg. colony-stimulating factor (CSF)、Erythropoietin(EPO) within 2 weeks.
5. Radiotherapy within 3 months.
6. Major surgery within 28 days
7. History of tumor vaccine treatment.
8. Live-virus (live attenuated) vaccine treatment within 28 days
9. High dose of steroid treatment (hydroprednisone >10mg/day or relevant dose of other drugs)
10. Patients with history of hematopoietic stem cell transplantation or planning to receive hematopoietic stem cell transplantation within 3 months.
11. Patients with history of Gastrointestinal perforation and/or fistula within 6 months.
12. Lymphoma in CNS, ADIS related lymphoma
13. Active infection by bacteria,virus,fungus which required hospitalization or severe infection required intravenous administration of antibiotics

14. Concomitant severe disease including but not limited to:

    • Known HIV or ADIS related disease
    • Asthma or interstitial lung disease or severe COPD
    • Myocardial infarction, unstable angina, Cardiovascular interventional surgery, Congestive heart failure(CHF; NYHA Grade II-IV), symptomatic or poorly controlled arrhythmia within 6 months before enrolling
    • The systolic pressure ≥140mmHg,or diastolic pressure≥90mmHg post treatment.
    • Acute or chronic hypotension(<90/60mmHg)
    • History of toxic epidermal necrolysis or Stevens-Johnson syndrome
    • Rheumatoid arthritis Granulomatous angiitis or microscopic polyangiitis
    • Ileus or history of following disease: inflammatory bowel disease or extensive intestinal resection(extensive bowel resection or hemicolectomy, combining chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea.
    • Previous or concomitant malignant, except basal-cell carcinoma or squamous cell carcinoma and/or cervical carcinoma in situ or effectively treated hematological malignancy and solid tumor that has been remission for more than 3 years and is considered to be cured.
    • Any history may affect the study result: increasing dosing risk or affect lab values and Judgment by the investigator that the patient should not participate in the study,
15. HBsAg positive; HBcAb positive and HBV-DNA≥upper limit of detection, HCV positive; HIV positive
16. Allergy to humanized antibody or human-mouse chimeric antibody.
17. Woman who are breast feeding or pregnant
18. Judgment by the investigator that the patient should not participate in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B001,B001 dose escalation; 5 groups with different dose: 350mg/700mg/1000mg/1500mg/2000mg	Biological: B001; 4 times intravenous injection totally,dosing at Day1,Day35,Day56,Day77

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of B001 as assessed by adverse reactions and events	Incidence and intensity of adverse events according to NCI CTCAE 4.03 associated with increasing doses of B001	42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration-time curve of B001	Measure the concentration of B001 in serum at different time point to get a concentration-time curve.	112 days
PD results of B001	Measure the number of CD19 positive B cell in peripheral blood	112 days
Immunogenicity of B001	Content analysis of anti-B001 antibody	112 days
ORR of B001	Objective response rate according to Response Criteria for Lymphoma（not including PET）and CLL Response Criteria	112 days

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Investigators: Principal Investigator: Lugui Qiu, Doctor, institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Principal Investigator: Junyuan Qi, Doctor, institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): February 28, 2021

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 15, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: B001-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No