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 |
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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
Plain English summary of protocol
Contact information
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 design | Multicentre non-randomised interventional screening and treatment trial |
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Primary study design | Interventional |
Secondary study design | Non randomised controlled trial |
Study setting(s) | GP practice |
Study type | Treatment |
Participant information sheet | Not available in web format, please contact marall@qmcr.qmul.ac.uk to request a patient 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 |
Pharmaceutical study type(s) | |
Phase | Phase I/II |
Drug / device / biological / vaccine name(s) | 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 study start date | 06/01/2010 |
Completion date | 09/10/2011 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Sex | Both |
Target number of participants | Planned sample size: 55; UK sample size: 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
- England
- United Kingdom
Study participating centre
EC1M 6BQ
United Kingdom
Sponsor information
University/education
Mile End Road
London
E1 4NS
England
United Kingdom
Website | http://www.qmul.ac.uk/ |
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https://ror.org/026zzn846 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
No information available
Results and Publications
Intention to publish date | |
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Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not provided at time of registration |
IPD sharing plan | Not provided at time of registration |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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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.