AzTrials
AzTrials

CancerPhase 1NCT01561911

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

A Phase 1 study testing Chi Lob 7/4 (A chimeric monoclonal antibody) in people with Cancer and Neoplasms, run by Cancer Research UK at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Neoplasms, Lymphoma
What is being tested?
Chi Lob 7/4 (A chimeric monoclonal antibody)
How many people
29 participants
Where
2 sitesUnited Kingdom
Study dates
Jul 2007to Oct 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.)
Show all 17Show fewer
  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Cancer Research UK Institute for Cancer Studies, University of Birmingham

    Edgbaston, Birmingham, B15 2TT

  • Cancer Research UK Medical Oncology Unit, Southampton General Hospital

    Tremona Road,, Southampton, SO16 6YD

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
Chi Lob 7/4 (A chimeric monoclonal antibody)
Keywords
Clinical Trial, Phase I, Antibodies, Monoclonal
Medical subject headings
Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chi Lob 7/4 (A chimeric monoclonal antibody)Drug

    3 patients will receive treatment at each dose level. Escalation from one treatment dose level to another will only be permitted once at least 3 patients have completed treatment without any DLTs. Starting weekly dose of Chi Lob 7/4 will be 0.5mg (giving a total dose per patient of 2mg divided over 4 weeks). Subsequent individual, weekly dose levels of 1.6mg, 5mg, 16mg, 50mg and 160mg (resulting in total patient doses of 6.4mg, 20mg, 64mg 200mg and 640mg respectively). Further dose escalation can continue to 240mg and 320mg dose per week (resulting in 960mg and 1280mg. Patients may be treated at a lower or intermediate dose level to define the MTD/BAD.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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. 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. 3. To determine the toxicity profile of Chi Lob 7/4 (CTCAE version 3.0) and to identify the dose limiting toxicity

  4. 4. To propose a safe dose for Phase II evaluation

Secondary outcomes (3)

  1. 1. To examine the Biological effects of ChiLob 7/4 Treatment

  2. 2. To examine the Pharmacokinetics of ChiLob 7/4 treatment: (Measurement of Serum Chi Lob 7/4)

  3. 3. To examine the Possible Anti-Tumour activity of Chi Lob 7/4 (RECIST 1.0 criteria)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2012 (estimated)
  2. Study startJul 2007
  3. Primary completionOct 2014
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01561911
Sponsor's protocol ID
PH1/103
Status last verified
Dec 2014
First submitted
21 Mar 2012
Last updated
2 Dec 2014
Results posted
No

Publications

  • Johnson P, Challis R, Chowdhury F, Gao Y, Harvey M, Geldart T, Kerr P, Chan C, Smith A, Steven N, Edwards C, Ashton-Key M, Hodges E, Tutt A, Ottensmeier C, Glennie M, Williams A. Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer Research UK phase I study. Clin Cancer Res. 2015 Mar 15;21(6):1321-8. doi: 10.1158/1078-0432.CCR-14-2355. Epub 2015 Jan 14.

    PubMed 25589626

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Chi Lob 7/4 (A chimeric monoclonal antibody) in people with Cancer and Neoplasms, run by Cancer Research UK at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1. To establish the Maximum tolerated dose (MTD)of ChiLob 7/4 ;. The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01561911, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in