Contact information
Additional identifiers
EudraCT number
2008-002286-32
ClinicalTrials.gov number
NCT01279707
Protocol/serial number
7566
Study information
Scientific title
Phase I/II study combining humanised anti-CD20 (veltuzumab), anti-CD22 (epratuzumab) or both monoclonal antibodies with intensive chemotherapy in adults with recurrent B-precursor acute lymphoblastic leukaemia (ALL)
Acronym
MARALL
Study hypothesis
This is a phase I/II study to determine the safety and tolerability of the combination of veltuzumab and epratzumab with intensive chemotherapy in patients with relapsed B-cell acute lymphoblastic leukaemia (ALL). A maximum of 55 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 UKALL XII + veltuzumab; a second, UKALL XII + epratuzumab and if limited toxicity is found in these first two groups, a third group will receive, UKALL XII + 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.
Ethics approval
North London REC 3 approved on the 10th August 2009 (ref: 09/H0709/42)
Study design
Multicentre non-randomised interventional screening and treatment trial
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please contact marall@qmcr.qmul.ac.uk to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute lymphoblastic)
Intervention
Cohort A patients:
1. UKALL 12 chemotherapy
2. Veltuzumab at 200 mg/m^2 intravenously on days 8 (as a 2-hour infusion), 15, 22 and 29 (as a 1-hour infusion)
Cohort B patients:
1. UKALL 12 chemotherapy
2. Epratuzumab at 360 mg/m^2 intravenously on days 8, 15, 22, 29 (as a 1-hour infusion)
Cohort C patients:
1. UKALL 12 chemotherapy
2. Epratuzumab and veltuzumab at 360 mg/m^2 and 200 mg/m^2 respectively, intravenously on days 8, 15, 22, 29.
All patients will receive UKALL 12 chemotherapy as shown below:
1. Daunorubicin given at 60 mg/m^2 intravenously on days 1, 8, 15 and 22
2. Dexamethasone given at 10 mg/m^2 orally on days 1 - 5 and days 11 - 14
3. L-asparaginase given at 5,000 iU/m^2 intravenously or intramuscularly on days 17, 19, 21, 23, 25, 27 and 29
4. Methotrexate 12.5 mg given intrathecally on day 24 only (unless central nervous system [CNS] leukaemia detected at relapse)
5. Vincristine given at 1.4 mg/m^2 intravenously on days 1, 8, 15 and 22
Follow-up length: 1 months
Study entry: registration only
Intervention type
Drug
Phase
Phase I/II
Drug names
Veltuzumab, epratzumab
Primary outcome measure
Assess the safety and tolerability of the combination of veltuzumab and/or epratuzumab with intensive chemotherapy for recurrent adult B-precursor ALL by scoring dose limiting toxicity events in patients.
Secondary outcome measures
Achievement of morphological and molecular complete remission on Day 29 bone marrow
Overall trial start date
06/01/2010
Overall trial end date
09/10/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged between 16 and 65 years, either sex
2. Confirmed diagnosis of first recurrence of B-precursor ALL (according to the World Health Organization [WHO] classification)
3. First complete remission (CR1) greater than 6 months
4. WHO/Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and well enough to receive intensive combination chemotherapy
5. 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 amenorrhoic for at least 24 months.
6. Patients must have a cardiac ejection fraction of greater than 50%
7. Patients must have adequate organ function:
7.1. Renal function serum creatinine less than 2.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) greater than 50 ml/min (measured EDTA or estimated creatinine clearance, e.g., Cockcroft & Gault)
7.2. Liver function - bilirubin/alanine aminotransferase (ALT) less than 2.5 x ULN
8. Patients must be able to comply with the study schedule
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned sample size: 55; UK sample size: 55
Participant exclusion criteria
1. Patients with Philadelphia positive (Ph +ve) ALL
2. Patients at 2nd or greater relapse of their ALL
3. Patients should not have received chemotherapy for relapsed ALL (except corticosteroids for a maximum of 5 days, before joining the study)
4. Patients who have already received greater than 340 mg/m^2 daunorubicin (or equivalent total anthracycline dose) therapy
5. Patients who have received prior mediastinal radiotherapy
6. 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
7. Patients with severe psychiatric disorders which in the PI's opinion makes them unsuitable for trial participation
8. 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 post-menopausal (that is amenorrheic for 24 months).
9. Females of childbearing potential must have a negative pregnancy test within 7 days prior to starting the study
10. Females must not be breastfeeding
11. Patients may not receive any other investigational agent during the study
12. Patients should not have received any antibody therapy within 9 months of joining this study
Recruitment start date
06/01/2010
Recruitment end date
09/10/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Centre for Experimental Cancer Medicine
London
EC1M 6BQ
United Kingdom
Sponsor information
Organisation
Queen Mary University of London
Sponsor details
Mile End Road
London
E1 4NS
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C1574/A9768)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Immunomedics Inc (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list