Recurrent or Refractory B Cell Acute Lymphoblastic LeukaemiaPhase 1/2MARALLNCT01279707
Monoclonal Antibodies in Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (MARALL)
A Phase 1/2 study testing humanised monoclonal antibody, veltuzumab, humanised monoclonal antibody epratuzumab and humanised monoclonal antibodies veltuzumab and epratuzumab in people with Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia, run by Queen Mary University of London at 10 sites in United Kingdom.
Trial summary
The treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades, particularly due to intensification of chemotherapies, improved supportive care and the incorporation of stem cell transplantation. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia
- What is being tested?
- humanised monoclonal antibody, veltuzumab, humanised monoclonal antibody epratuzumab and humanised monoclonal antibodies veltuzumab and epratuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- Jan 2010to Aug 2014
- Phase
- Phase 1/2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Aged 16 years or over
- Confirmed diagnosis of recurrent or refractory B-precursor ALL [according to the WHO classification].
- Greater than 5% blasts in the bone marrow
- WHO/ECOG performance status of 0-2 and well enough to receive intensive combination chemotherapy.
- Negative pregnancy test in women of childbearing potential. Women will not be considered of child bearing potential if they have undergone surgical removal of the uterus or are post menopausal and have been amenorrhoeic for at least 24 months.
- Patients must have adequate organ function:
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- Renal function - serum creatinine <2.5 x ULN or eGFR>50ml/min (measured EDTA or estimated creatinine clearance e.g Cockcroft \& Gault)
- Liver function (bilirubin/ALT <2.5 x ULN)
- Patients must be able to comply with the study schedule.
Who cannot join
- Patients should not have received chemotherapy for current episode of relapsed ALL (except corticosteroids for a maximum of 10 days, before joining the study).
- Patients with co-morbidities: e.g. uncontrolled hypertension and or poorly controlled diabetes which in the PI's opinion makes them unsuitable for the study.
- Patients with severe psychiatric disorders which in the PI's opinion makes them unsuitable for trial participation.
- Females of childbearing potential and all males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) for the duration of the study and for up to 3 months after the last dose of study medication. Note: Subjects are not considered of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to starting the study.
- Females must not be breastfeeding.
- Patients may not receive any other investigational agent during the study.
- Patients should not have received any antibody therapy within 3 months of joining this study.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
University Hospitals Birmingham NHS Foundation
Birmingham, B15 2TH
University of Bristol Foundation Trust
Bristol, BS2 8BJ
University Hospital of Wales
Cardiff, CF14 4XN
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Barts and the London NHS Trust
London, EC1A 7BE
Royal Free Hampstead NHS Trust
London, NW3 2QG
Newcastle University
Newcastle, NE2 4HH
Nottingham City Hospital
Nottingham, NG5 1PB
Plymouth Hospitals NHS Trust
Plymouth, PL6 8DH
About this study
Official title: Phase I/II Study Combining Humanised Anti-CD20 (Veltuzumab), Anti-CD22 (Epratuzumab) and Both Monoclonal Antibodies With Intensive Chemotherapy in Adults With Recurrent or Refractory B-precursor Acute Lymphoblastic Leukaemia (ALL)
The treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades, particularly due to intensification of chemotherapies, improved supportive care and the incorporation of stem cell transplantation. However, the maximum tolerability of standard chemotherapeutics has been reached in ALL. Using conventional chemotherapy, 80-85% of adults with ALL will achieve a complete remission (CR). Unfortunately treatment at relapse is generally unsuccessful and rarely results, in long-term survival (7% survival at 5 years). Therefore, the investigators are exploring novel treatment strategies through the use of monoclonal antibodies (MoAbs) directed at surface antigens on leukaemic blasts. Using MoAbs directed against surface proteins on B cells has had excellent results in other B-cell diseases such as low and high grade non-Hodgkin lymphomas, without additional toxicity. There has also been limited evidence from small studies and case reports of the efficacy of MoAbs in ALL.
This is a Phase I/II study to determine the safety and tolerability of the combination of veltuzumab and epratuzumab with intensive chemotherapy in patients with relapsed B-cell ALL. A maximum of 51 patients will be treated with a combination of UKALL XII induction chemotherapy and the monoclonal antibodies veltuzumab and epratuzumab. Veltuzumab and epratuzumab are humanised monoclonal antibodies that target CD20 and CD22 surface proteins, respectively. Both of these proteins are expressed on ALL tumour B cells.
One group of patients will receive modified UKALL XII chemotherapy + veltuzumab; a second, modified UKALL XII chemotherapy + epratuzumab and if limited toxicity is found in these first 2 groups, a third group will receive, modified UKALL XII chemotherapy + both veltuzumab and epratuzumab. Patients will be assessed for safety, tolerability and disease response. Safety and tolerability will be measured by the number of Dose Limiting Toxicities (DLTs) in each group. Disease response will be measured by the microscopic appearance of patient bone marrow samples at day 29, and by molecular tests for tumour cells in bone marrow.
- Being tested
- humanised monoclonal antibody, veltuzumab, humanised monoclonal antibody epratuzumab, humanised monoclonal antibodies veltuzumab and epratuzumab
- Medical subject headings
- Recurrence, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
humanised monoclonal antibody, veltuzumabBiological
Veltuzumab with modified UKALL XII induction chemotherapy. Veltuzumab will be administered at 200 mg/m2 IV on Day 8 and subsequently, (if tolerated on Day 8), over 1 hour on Days 15, 22, 29.
humanised monoclonal antibody epratuzumabBiological
Epratuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29.
humanised monoclonal antibodies veltuzumab and epratuzumabBiological
Epratuzumab + Veltuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29. Veltuzumab will be administered at 200 mg/m2 IV over 2 hours on Day 8 and over 1 hour on Days 15, 22 and 29. Veltuzumab will be infused 1 hour after the infusion of epratuzumab.
| Study group | Role | What they receive |
|---|---|---|
| A: Veltuzumab and chemotherapy | Experimental | Veltuzumab and modified UKALL XII chemotherapy Receives: Biological: humanised monoclonal antibody, veltuzumab |
| B: epratuzumab and chemotherapy | Experimental | epratuzumab and modified UKALL XII chemotherapy Receives: Biological: humanised monoclonal antibody epratuzumab |
| C: veltuzumab and epratuzumab and chemotherapy | Experimental | Veltuzumab and Epratuzumab and modified UKALL XII chemotherapy Receives: Biological: humanised monoclonal antibodies veltuzumab and epratuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The total number of dose limiting toxicity events (DLTs) to measure safety and tolerability
The primary objective is to assess the safety and tolerability of the combination of veltuzumab and/or epratuzumab with intensive chemotherapy for recurrent or refractory adult B-precursor ALL.
Measured: Day 29
Secondary outcomes (1)
Morphological and molecular remission in bone marrow
Achievement of morphological complete remission on Day 29 bone marrow
Efficacy of treatment to achieve MRD negativity, and investigate a possible association between the intensity of CD20 and CD22 antigen expression and treatment activity.
Measured: Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2011 (estimated)
- Study startJan 2010
- Primary completionAug 2014 (estimated)
- Study completionAug 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent or Refractory B Cell Acute Lymphoblastic LeukaemiaStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Matthew Smith, Doctor, Principal investigator, Barts and The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01279707
- Sponsor's protocol ID
- 6125
- Acronym
- MARALL
- Status last verified
- Jul 2014
- First submitted
- 12 Apr 2010
- Last updated
- 14 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study Combining Humanised Anti-CD20 (Veltuzumab), Anti-CD22 (Epratuzumab) and Both Monoclonal Antibodies With Intensive Chemotherapy in Adults With Recurrent or Refractory B-precursor Acute Lymphoblastic Leukaemia (ALL)
- ClinicalTrials.gov ID
- NCT01279707
- Acronym / sponsor ID
- MARALL / 6125
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Jan 2010
- Primary completion
- Aug 2014 (estimated)
- Study completion
- Aug 2014 (estimated)
- First posted
- 19 Jan 2011 (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 treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades, particularly due to intensification of chemotherapies, improved supportive care and the incorporation of stem cell transplantation. However, the maximum tolerability of standard chemotherapeutics has been reached in ALL. Using conventional chemotherapy, 80-85% of adults with ALL will achieve a complete remission (CR). Unfortunately treatment at relapse is generally unsuccessful and rarely results, in long-term survival (7% survival at 5 years). Therefore, the investigators are exploring novel treatment strategies through the use of monoclonal antibodies (MoAbs) directed at surface antigens on leukaemic blasts. Using MoAbs directed against surface proteins on B cells has had excellent results in other B-cell diseases such as low and high grade non-Hodgkin lymphomas, without additional toxicity. There has also been limited evidence from small studies and case reports of the efficacy of MoAbs in ALL.
This is a Phase I/II study to determine the safety and tolerability of the combination of veltuzumab and epratuzumab with intensive chemotherapy in patients with relapsed B-cell ALL. A maximum of 51 patients will be treated with a combination of UKALL XII induction chemotherapy and the monoclonal antibodies veltuzumab and epratuzumab. Veltuzumab and epratuzumab are humanised monoclonal antibodies that target CD20 and CD22 surface proteins, respectively. Both of these proteins are expressed on ALL tumour B cells.
One group of patients will receive modified UKALL XII chemotherapy + veltuzumab; a second, modified UKALL XII chemotherapy + epratuzumab and if limited toxicity is found in these first 2 groups, a third group will receive, modified UKALL XII chemotherapy + both veltuzumab and epratuzumab. Patients will be assessed for safety, tolerability and disease response. Safety and tolerability will be measured by the number of Dose Limiting Toxicities (DLTs) in each group. Disease response will be measured by the microscopic appearance of patient bone marrow samples at day 29, and by molecular tests for tumour cells in bone marrow.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A: Veltuzumab and chemotherapy | Experimental | Biological: humanised monoclonal antibody, veltuzumabVeltuzumab and modified UKALL XII chemotherapy |
| B: epratuzumab and chemotherapy | Experimental | Biological: humanised monoclonal antibody epratuzumabepratuzumab and modified UKALL XII chemotherapy |
| C: veltuzumab and epratuzumab and chemotherapy | Experimental | Biological: humanised monoclonal antibodies veltuzumab and epratuzumabVeltuzumab and Epratuzumab and modified UKALL XII chemotherapy |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 16 years or over
- Confirmed diagnosis of recurrent or refractory B-precursor ALL [according to the WHO classification].
- Greater than 5% blasts in the bone marrow
- WHO/ECOG performance status of 0-2 and well enough to receive intensive combination chemotherapy.
- Negative pregnancy test in women of childbearing potential. Women will not be considered of child bearing potential if they have undergone surgical removal of the uterus or are post menopausal and have been amenorrhoeic for at least 24 months.
Key exclusion criteria (8 listed)
- Patients should not have received chemotherapy for current episode of relapsed ALL (except corticosteroids for a maximum of 10 days, before joining the study).
- Patients with co-morbidities: e.g. uncontrolled hypertension and or poorly controlled diabetes which in the PI's opinion makes them unsuitable for the study.
- Patients with severe psychiatric disorders which in the PI's opinion makes them unsuitable for trial participation.
- Females of childbearing potential and all males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) for the duration of the study and for up to 3 months after the last dose of study medication. Note: Subjects are not considered of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to starting the study.
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 |
|---|---|---|
| humanised monoclonal antibody, veltuzumabVeltuzumab with modified UKALL XII induction chemotherapy. Veltuzumab will be administered at 200 mg/m2 IV on Day 8 and subsequently, (if tolerated on Day 8), over 1 hour on Days 15, 22, 29. | Biological | A: Veltuzumab and chemotherapy |
| humanised monoclonal antibody epratuzumabEpratuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29. | Biological | B: epratuzumab and chemotherapy |
| humanised monoclonal antibodies veltuzumab and epratuzumabEpratuzumab + Veltuzumab with modified UKALL XII induction chemotherapy. Epratuzumab will be administered at 360 mg/m2 IV over 1 hour on Days 8, 15, 22 and 29. Veltuzumab will be administered at 200 mg/m2 IV over 2 hours on Day 8 and over 1 hour on Days 15, 22 and 29. Veltuzumab will be infused 1 hour after the infusion of epratuzumab. | Biological | C: veltuzumab and epratuzumab and chemotherapy |
Primary outcome
The total number of dose limiting toxicity events (DLTs) to measure safety and tolerability
Time frame: Day 29
The primary objective is to assess the safety and tolerability of the combination of veltuzumab and/or epratuzumab with intensive chemotherapy for recurrent or refractory adult B-precursor ALL.
1 secondary outcome
Morphological and molecular remission in bone marrow
Time frame: Day 29
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2014.
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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.
Matthew Smith, Doctor principal investigator
Barts and The London NHS Trust
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing humanised monoclonal antibody, veltuzumab, humanised monoclonal antibody epratuzumab and humanised monoclonal antibodies veltuzumab and epratuzumab in people with Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia, run by Queen Mary University of London at 10 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 8 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: status not confirmed, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
The total number of dose limiting toxicity events (DLTs) to measure safety and tolerability (time frame: Day 29). 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 14 Jul 2014.