Safety and tolerability of the combination of veltuzumab and epratuzumab with intensive chemotherapy in patients with relapsed B-cell acute lymphoblastic leukaemia (ALL)

ISRCTN	ISRCTN15257573
DOI	https://doi.org/10.1186/ISRCTN15257573
ClinicalTrials.gov (NCT)	NCT01279707
Clinical Trials Information System (CTIS)	2008-002286-32
Protocol serial number	7566
Sponsor	Queen Mary University of London
Funders	Cancer Research UK (CRUK) (UK) (ref: C1574/A9768), Immunomedics Inc (USA)

Submission date: 12/05/2010
Registration date: 12/05/2010
Last edited: 24/03/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-study-adding-biological-therapy-chemotherapy-acute-lymphoblastic-leukaemia-come-back-after-treatment-marall

Contact information

Ms Joanne Meerabux
Scientific

Centre for Experimental Cancer Medicine
Institute of Cancer
Barts and The London School of Medicine and Dentistry
Lower Ground Floor Old Anatomy Building
Charterhouse Square
London
EC1M 6BQ
United Kingdom

Study information

Primary study design	Interventional
Study design	Multicentre non-randomised interventional screening and treatment trial
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
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)
Study acronym	MARALL
Study objectives	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(s)	North London REC 3 approved on the 10th August 2009 (ref: 09/H0709/42)
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Veltuzumab, epratzumab
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	Achievement of morphological and molecular complete remission on Day 29 bone marrow
Completion date	09/10/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	55
Total final enrolment	27
Key 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
Key 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
Date of first enrolment	06/01/2010
Date of final enrolment	09/10/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Centre for Experimental Cancer Medicine

London
EC1M 6BQ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			24/03/2022	No	Yes

Editorial Notes

24/03/2022: Plain English results added.
20/05/2019: The total final enrolment was added.
08/03/2019: A link was added to the basic results (scientific) field.
26/03/2018: No publications found, verifying study status with principal investigator.
10/02/2015: No publications found, verifying study status with principal investigator.