A Phase I Study of the Chimeric Anti-CD40 Monoclonal Antibody ChiLob 7/4 to Treat Advanced Malignancies Refractory to Conventional Anti-cancer Treatment

December 1, 2014 updated by: Cancer Research UK

A Phase I Clinical Research Study Evaluating the Safety, Tolerability and Biological Effects of the Chimeric Anti-CD40 Monoclonal Antibody Chi Lob 7/4 Given Intravenously, Weekly for Four Weeks in the Treatment of Patients With Advanced Malignancies Refractory to Conventional Anti-cancer Treatment.

The Purpose of this study is to evaluate the safety and tolerability, and the biological effects of the chimeric anti-CD40 monoclonal antibody Chi Lob 7/4, given intravenously, weekly for 4 weeks in the treatment of patients with advanced malignancies refractory to conventional anti-cancer treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The primary objective of the study is to establish the safety and maximum tolerated dose of Chi Lob 7/4. In line with other established antineoplastic, chimeric monoclonal antibody therapies such as Rituximab, Chi Lob 7/4 will be given by slow intravenous infusion once every week for a total of four weeks. This treatment regimen will facilitate early, rapid and dose dense administration of antibody to a patient group with advanced malignancy refractory to conventional treatment. The starting dose for each infusion of Chi Lob 7/4 will be 0.5mg (giving a total dose per patient of 2mg divided over 4 weeks). Escalation from one treatment dose level to another will only be permitted when at least 3 patients have completed treatment without dose limiting toxicity.

Study Type

Interventional

Enrollment (Actual)

29

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 Locations

  • United Kingdom
    • Birmingham
      • Edgbaston, Birmingham, United Kingdom, B15 2TT
        • Cancer Research UK Institute for Cancer Studies, University of Birmingham
    • Southampton
      • Tremona Road,, Southampton, United Kingdom, SO16 6YD
        • Cancer Research UK Medical Oncology Unit, Southampton General Hospital

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically proven CD40 expressing solid tumours or diffuse large B-cell non-Hodgkin"s lymphoma refractory to conventional treatment, or for which no conventional therapy exists.
  • Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented.
  • Age greater than 18 years.
  • Life expectancy of at least 12 weeks.
  • World Health Organisation (WHO) performance status of 0-1 (Appendix 1).

  • Haematological and biochemical indices (These measurements must be performed within one week prior to the patient going on study.)

    • Haemoglobin (Hb) ≥ 9.0 g/dl
    • Neutrophils ≥ 1 x 10^9/L
    • Total Lymphocyte count ≥ 0.5 x 10^9/L
    • Platelets (Plts) ≥ 75 x 10^9/L

    • The following baseline liver function tests :

      • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
      • Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) ≤ 3 x ULN unless due to tumour in which case up to 5 x ULN is permissible

    • The following baseline renal function test:

      • calculated creatinine clearance ≥ 40 mL/min (uncorrected value) or isotope clearance measurement ≥ 40mL/min
  • Female patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test prior to enrolment and agree to use appropriate medically approved contraception for four weeks prior to entering the trial, during the trial and for six months afterwards.
  • Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards.

Exclusion Criteria:

  • CD40 negative tumours by immunohistochemistry.
  • Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas and mitomycin-C) prior to treatment.
  • All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities which in the opinion of the Investigator and Cancer Research UK should not exclude the patient.
  • Pregnant and lactating women are excluded.
  • Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not yet recovered.
  • Patients with primary brain tumours or clinically apparent brain metastases.
  • Patients who are high medical risks because of non-malignant systemic disease including active uncontrolled infection.
  • Patients with any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial.
  • Patients known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
  • Long term immunosuppression or steroids (for more than one month)
  • History of significant and serious allergy.
  • Concurrent congestive heart failure or prior history of class III/ IV cardiac disease (New York Heart Association [NYHA] - refer to Appendix 4)
  • Patients with low grade or transformed non-Hodgkin"s lymphoma.
  • Prior treatment with murine monoclonal antibodies. (Prior treatment with chimeric or fully human antibodies will not exclude a patient).
  • A history of clinically significant autoimmune disease.
  • Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.

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

  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
1. To establish the Maximum tolerated dose (MTD)of ChiLob 7/4 ;
Defined as the dose below the dose at which no more 30% (2 of up to 6 patients in the cohort) , experienced a DLT (Dose Limiting Toxicity) due to ChiLob 7/4 occurring during the treatment period and up to 4 week's post treatment.
2. To determine the Biologically Active Dose of Chi Lob 7/4, which is defined as the dose level at which peripheral blood B-cells are reduced by the end of therapy to 10% or less of the starting number.
3. To determine the toxicity profile of Chi Lob 7/4 (CTCAE version 3.0) and to identify the dose limiting toxicity
4. To propose a safe dose for Phase II evaluation

Secondary Outcome Measures

Outcome Measure
1. To examine the Biological effects of ChiLob 7/4 Treatment
2. To examine the Pharmacokinetics of ChiLob 7/4 treatment: (Measurement of Serum Chi Lob 7/4)
3. To examine the Possible Anti-Tumour activity of Chi Lob 7/4 (RECIST 1.0 criteria)

Collaborators and Investigators

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

Sponsor

Cancer Research UK

Investigators

  • Principal Investigator: Peter W Johnson, Professor, Cancer Research UK Medical Oncology Unit, Southampton General Hospital,

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

July 1, 2007

Primary Completion (ACTUAL)

October 1, 2014

Study Completion (ACTUAL)

October 1, 2014

Study Registration Dates

First Submitted

March 21, 2012

First Submitted That Met QC Criteria

March 22, 2012

First Posted (ESTIMATE)

March 23, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

December 2, 2014

Last Update Submitted That Met QC Criteria

December 1, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PH1/103

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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