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.
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Cancer
- Sponsor
- Cancer Research UK
- Enrollment
- 29
- Locations
- 2
- Primary Endpoint
- 4. To propose a safe dose for Phase II evaluation
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
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
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)
Outcomes
Primary Outcomes
4. To propose a safe dose for Phase II evaluation
3. To determine the toxicity profile of Chi Lob 7/4 (CTCAE version 3.0) and to identify the dose limiting toxicity
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.
Secondary Outcomes
- 3. To examine the Possible Anti-Tumour activity of Chi Lob 7/4 (RECIST 1.0 criteria)
- 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)