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
EudraCT/CTIS number 2008-002286-32
ClinicalTrials.gov number NCT01279707
Secondary identifying numbers 7566
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

Study designMulticentre non-randomised interventional screening and treatment trial
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)GP practice
Study typeTreatment
Participant information sheet Not available in web format, please contact marall@qmcr.qmul.ac.uk to request a patient information sheet
Scientific titlePhase 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 acronymMARALL
Study objectivesThis 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) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute lymphoblastic)
InterventionCohort 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)Veltuzumab, epratzumab
Primary outcome measureAssess 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 measuresAchievement of morphological and molecular complete remission on Day 29 bone marrow
Overall study start date06/01/2010
Completion date09/10/2011

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsPlanned sample size: 55; UK sample size: 55
Total final enrolment27
Key inclusion criteria1. 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 criteria1. 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 enrolment06/01/2010
Date of final enrolment09/10/2011

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Centre for Experimental Cancer Medicine
London
EC1M 6BQ
United Kingdom

Sponsor information

Queen Mary University of London
University/education

Mile End Road
London
E1 4NS
England
United Kingdom

Website http://www.qmul.ac.uk/
ROR logo "ROR" https://ror.org/026zzn846

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C1574/A9768)
Private sector organisation / Other non-profit organizations
Alternative name(s)
CR_UK, Cancer Research UK - London, CRUK
Location
United Kingdom
Immunomedics Inc (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

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

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.