Indolent B-cell LymphomaPhase 1NCT01805375
A Phase I Trial of DI-B4 in Patients With Advanced CD19 Positive Indolent B-cell Malignancies
A Phase 1 study testing DI-B4 in people with Indolent B-cell Lymphoma and Chronic Lymphocytic Leukaemia, run by Cancer Research UK at 5 sites in United Kingdom.
Trial summary
The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed. The study will also look at what happens to Anti-CD19 (DI-B4) inside the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Indolent B-cell Lymphoma, Chronic Lymphocytic Leukaemia, Waldenström Macroglobulinaemia
- What is being tested?
- DI-B4
- Type of treatment
- Injection or infusion
- How many people
- 28 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Apr 2013to 14 Dec 2017
- 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
- 1. Histologically proven relapsed or refractory indolent B-cell lymphoma or chronic lymphocytic leukaemia. Patients must have received at least one line of previous therapy.
- 2. CD19 positive malignancy as demonstrated by immunohistochemistry or flow cytometry
- 3. Life expectancy of at least 12 weeks
- 4. World Health Organisation (WHO) performance status of 0-1
- 5. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient commences treatment with DI-B4.
- Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL (red cell support is permissible), Absolute neutrophil count (ANC) ≥1.0 x 10^9/L (or ≥0.5 x 10^9/L if bone marrow involvement), Platelet count ≥75 x 10^9/L (or ≥30 x 10^9/L if bone marrow involvement), Serum bilirubin ≤1.5 x upper limit of normal (ULN), unless raised due to Gilbert's syndrome in which case up to 3 x ULN is permissible Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) ≤ 2.5 x (ULN) unless raised due to hepatic involvement in which case up to 5 x ULN is permissible
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- 6. 18 years or over
- 7. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up
- 8. Indolent B-cell lymphoma patients only: Patient has either at least one measurable lesion by CT scan (defined as >1.5 cm in one axis) or in the case of Waldenström's macroglobulinemia, disease must be assessable by the protocol criteria.
Who cannot join
- 1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy or investigational medicinal products during the previous 4 weeks before treatment.
- 2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
- 3. Known to be serologically positive for hepatitis B (unless due to vaccination), hepatitis C or human immunodeficiency virus (HIV).
- 4. Patients with clinically active leptomeningeal or central nervous system lymphoma/leukaemia.
- 5. Patients with transformed lymphoma from a pre-existing indolent lymphoma. Patients with a previous history of transformation, but on this disease episode have a biopsy proven indolent recurrence may be included.
- 6. Patients receiving corticosteroids, except where the patient has been on a stable dose for the preceding seven days. Doses of prednisolone or equivalent >10 mg daily are not permitted whilst on the study, doses up to 20mg can be taken any time prior to Cycle 1, Day 1
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- 7. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), history of unstable angina pectoris or myocardial infarction up to 1 year prior to patient enrolment into the trial, presence of severe valvular heart disease or presence of a ventricular arrhythmia requiring treatment
- 8. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the trial and for six months afterwards are considered eligible.
- 9. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
- 10. Major thoracic or abdominal surgery from which the patient has not yet recovered.
- 11. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
- 12. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I study of DI-B4. Participation in an observational trial would be acceptable.
- 13. Any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Royal Liverpool and Broadgreen University Hospital NHS Trust
Liverpool, L7 8XP
The Christie NHS Foundation Trust
Manchester, M20 4BX
The Churchill Hospital
Oxford, OX3 7LE
Derriford Hospital
Plymouth, PL6 8DH
University Hospital Southampton NHS Foundation Trust
Southampton, S016 6YD
About this study
Official title: A Cancer Research UK Phase I Trial of the Anti-CD19 DI-B4 Monoclonal Antibody Given Intravenously, Weekly for Four Weeks, in Patients With Advanced CD19 Positive Indolent B-cell Malignancies
The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed. The study will also look at what happens to Anti-CD19 (DI-B4) inside the body.
DI-B4 is a type of drug called an Anti-CD19 monoclonal antibody which is being used to stop the growth and kill cancerous immune cells by targeting the B-cell marker (CD-19) expressed on their surface. This drug has not been given to patients before.
Read more
DI-B4 will be given weekly by intravenous infusion for four weeks. The study is in two parts. In Part 1, small groups of patients will be treated at increasing doses to find the highest safest dose and best dose for part 2 of the study. Approximately 16-20 patients will be treated in this part. In Part 2, the dose identified in Part 1 will be given to approximately 20 patients.
Patients recruited to the study will receive four weeks (cycles) of treatment. They will attend an end of therapy visit eight weeks after their last dose of DI-B4, and attend follow-up visits up to eighteen months after their first dose of DI-B4. Information on the overall and progression free survival will be collected for a period up to eighteen months after the final patient is treated on the study.
Patients will have blood and urine samples taken each week during treatment amongst other clinical tests. CT scans will be performed at the start of the study, at eight weeks post treatment and six months after the study start. Bone marrow biopsies and FDG-PET scans will only be taken if needed. Research blood samples will also be taken to look at what happens to the drug inside the body.
It is important to explain that patients will have advanced cancer so it is unlikely that patients will benefit directly from taking part but the study may help improve future treatment of cancer.
Read the detailed description
Patients with relapsed or refractory CD19 positive indolent B-cell lymphoma, Waldenström Macroglobulinaemia or chronic lymphocytic leukaemia will be entered into this study.
For the vast majority of patients, B-cell non Hodgkin lymphoma and chronic lymphocytic leukaemia are incurable using existing therapeutic approaches.
Although anti-CD20 directed therapy has improved outcomes, more than fifty percent of patients still relapse following treatment or are refractory to it and therefore additional novel non-cross resistant therapies are urgently required.
DI-B4 is a humanised, low-fucosylated anti-CD19 Immunoglobulin (Ig) G1 monoclonal antibody with potent antibody-dependent cell-mediated cytotoxicity (ADCC) but minimal complement dependent cytotoxicity (CDC). The target antigen, CD19, is the canonical B-cell marker that is expressed on all B-cells including the malignant B-cells in NHL, CLL and acute lymphoblastic leukaemia (ALL). The CD19 antigen is therefore an attractive B-cell lineage specific target for monoclonal antibody therapy. DI-B4 is expected to act through the depletion of normal and malignant CD19 positive cells, primarily via ADCC.
This is a multi-centre, Phase I, dose escalation/dose expansion study. For the first three cohorts, an intra-patient dose escalation scheme will be followed unless a DLT is observed. From Cohort 4 onwards, a standard 3 + 3 dose escalation schedule of DI-B4 will be continued until the maximum tolerated dose (MTD) is defined, up to a maximum dose of 1000mg.
- Being tested
- DI-B4
- Keywords
- Phase I, Cancer, CD19 positive, B-Cell lymphoma, chronic lymphocytic leukaemia, Waldenström Macroglobulinaemia
- Medical subject headings
- Leukemia, B-Cell, Waldenstrom Macroglobulinemia, Neoplasms, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DI-B4Drug
DI-B4 will be administered once weekly for up to a total of four weeks. The starting dose will be 0.02 mg given as an intravenous infusion. A cycle is 1 week in duration and patients should expect to receive a maximum of 4 cycles.
What is being measured
The primary outcome is the main question the study is designed to answer.
To recommend a dose for future trials with a new drug called DI-B4 by finding the highest safe dose which can be given to patients
Measured: 38 Months
Secondary outcomes (5)
Measuring of PK parameter values for DI-B4 including AUC, Cmax, Tmax, and half life T1/2.
Measured: Samples taken during the four weeks of treatment and analysed in batches per cohort within 6 months of sampling
To evaluate the effect of DI-B4 on the depletion of peripheral blood and bone marrow B-cells.
Measured: Samples taken during the four weeks of treatment, and for 18 month follow-up and analysed in batches per cohort within 6 months of sampling
To look for signs of anti-tumour activity of DI-B4 in patients with relapsed or refractory indolent B-cell malignancies.
Measured: 38 months
To assess immunogenicity of DI-B4 in patients with relapsed or refractory indolent B-cell malignancies
Measured: 54 months
To measure the time to disease progression and eighteen month survival
Measured: 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2013 (estimated)
- Study startApr 2013
- Primary completion14 Dec 2017
- Study completion14 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Indolent B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01805375
- Sponsor's protocol ID
- CRUKD/12/003
- Status last verified
- Feb 2018
- First submitted
- 4 Mar 2013
- Last updated
- 5 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cancer Research UK Phase I Trial of the Anti-CD19 DI-B4 Monoclonal Antibody Given Intravenously, Weekly for Four Weeks, in Patients With Advanced CD19 Positive Indolent B-cell Malignancies
- ClinicalTrials.gov ID
- NCT01805375
- Acronym / sponsor ID
- CRUKD/12/003
- Keywords
- Phase I, Cancer, CD19 positive, B-Cell lymphoma, chronic lymphocytic leukaemia, Waldenström Macroglobulinaemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- 14 Dec 2017 (actual)
- Study completion
- 14 Dec 2017 (actual)
- First posted
- 6 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed. The study will also look at what happens to Anti-CD19 (DI-B4) inside the body.
DI-B4 is a type of drug called an Anti-CD19 monoclonal antibody which is being used to stop the growth and kill cancerous immune cells by targeting the B-cell marker (CD-19) expressed on their surface. This drug has not been given to patients before.
DI-B4 will be given weekly by intravenous infusion for four weeks. The study is in two parts. In Part 1, small groups of patients will be treated at increasing doses to find the highest safest dose and best dose for part 2 of the study. Approximately 16-20 patients will be treated in this part. In Part 2, the dose identified in Part 1 will be given to approximately 20 patients.
Patients recruited to the study will receive four weeks (cycles) of treatment. They will attend an end of therapy visit eight weeks after their last dose of DI-B4, and attend follow-up visits up to eighteen months after their first dose of DI-B4. Information on the overall and progression free survival will be collected for a period up to eighteen months after the final patient is treated on the study.
Patients will have blood and urine samples taken each week during treatment amongst other clinical tests. CT scans will be performed at the start of the study, at eight weeks post treatment and six months after the study start. Bone marrow biopsies and FDG-PET scans will only be taken if needed. Research blood samples will also be taken to look at what happens to the drug inside the body.
It is important to explain that patients will have advanced cancer so it is unlikely that patients will benefit directly from taking part but the study may help improve future treatment of cancer.
Detailed description
Patients with relapsed or refractory CD19 positive indolent B-cell lymphoma, Waldenström Macroglobulinaemia or chronic lymphocytic leukaemia will be entered into this study.
For the vast majority of patients, B-cell non Hodgkin lymphoma and chronic lymphocytic leukaemia are incurable using existing therapeutic approaches.
Although anti-CD20 directed therapy has improved outcomes, more than fifty percent of patients still relapse following treatment or are refractory to it and therefore additional novel non-cross resistant therapies are urgently required.
DI-B4 is a humanised, low-fucosylated anti-CD19 Immunoglobulin (Ig) G1 monoclonal antibody with potent antibody-dependent cell-mediated cytotoxicity (ADCC) but minimal complement dependent cytotoxicity (CDC). The target antigen, CD19, is the canonical B-cell marker that is expressed on all B-cells including the malignant B-cells in NHL, CLL and acute lymphoblastic leukaemia (ALL). The CD19 antigen is therefore an attractive B-cell lineage specific target for monoclonal antibody therapy. DI-B4 is expected to act through the depletion of normal and malignant CD19 positive cells, primarily via ADCC.
This is a multi-centre, Phase I, dose escalation/dose expansion study. For the first three cohorts, an intra-patient dose escalation scheme will be followed unless a DLT is observed. From Cohort 4 onwards, a standard 3 + 3 dose escalation schedule of DI-B4 will be continued until the maximum tolerated dose (MTD) is defined, up to a maximum dose of 1000mg.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1. Histologically proven relapsed or refractory indolent B-cell lymphoma or chronic lymphocytic leukaemia. Patients must have received at least one line of previous therapy.
- 2. CD19 positive malignancy as demonstrated by immunohistochemistry or flow cytometry
- 3. Life expectancy of at least 12 weeks
- 4. World Health Organisation (WHO) performance status of 0-1
- 5. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient commences treatment with DI-B4.
Key exclusion criteria (13 listed)
- 1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy or investigational medicinal products during the previous 4 weeks before treatment.
- 2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
- 3. Known to be serologically positive for hepatitis B (unless due to vaccination), hepatitis C or human immunodeficiency virus (HIV).
- 4. Patients with clinically active leptomeningeal or central nervous system lymphoma/leukaemia.
- 5. Patients with transformed lymphoma from a pre-existing indolent lymphoma. Patients with a previous history of transformation, but on this disease episode have a biopsy proven indolent recurrence may be included.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DI-B4DI-B4 will be administered once weekly for up to a total of four weeks. The starting dose will be 0.02 mg given as an intravenous infusion. A cycle is 1 week in duration and patients should expect to receive a maximum of 4 cycles. | Drug | – |
Primary outcome
To recommend a dose for future trials with a new drug called DI-B4 by finding the highest safe dose which can be given to patients
Time frame: 38 Months
5 secondary outcomes
Measuring of PK parameter values for DI-B4 including AUC, Cmax, Tmax, and half life T1/2.
Time frame: Samples taken during the four weeks of treatment and analysed in batches per cohort within 6 months of sampling
To evaluate the effect of DI-B4 on the depletion of peripheral blood and bone marrow B-cells.
Time frame: Samples taken during the four weeks of treatment, and for 18 month follow-up and analysed in batches per cohort within 6 months of sampling
To look for signs of anti-tumour activity of DI-B4 in patients with relapsed or refractory indolent B-cell malignancies.
Time frame: 38 months
To assess immunogenicity of DI-B4 in patients with relapsed or refractory indolent B-cell malignancies
Time frame: 54 months
To measure the time to disease progression and eighteen month survival
Time frame: 54 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DI-B4 in people with Indolent B-cell Lymphoma and Chronic Lymphocytic Leukaemia, run by Cancer Research UK at 5 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 9 inclusion and 13 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 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
To recommend a dose for future trials with a new drug called DI-B4 by finding the highest safe dose which can be given to patients (time frame: 38 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2018.