BLAM- A phase IIb study of Blinatumomab + Cytarabine (AraC) and Methotrexate in adult B-precursor Acute Lymphoblastic Leukaemia

• Register: ANZCTR
• Last refreshed on: 15 April 2024
• Main ID: ACTRN12617000084381
• Date of registration: 16/01/2017
• Prospective Registration: Yes
• Primary sponsor: Australasian Leukaemia and Lymphoma Group
• Public title: BLAM- A phase IIb study of Blinatumomab + Cytarabine (AraC) and Methotrexate in adult B-precursor Acute Lymphoblastic Leukaemia
• Scientific title: BLAM- A phase IIb study of Blinatumomab + Cytarabine (AraC) and Methotrexate in adult B-precursor Acute Lymphoblastic Leukaemia
• Date of first enrolment: 17/05/2018
• Target sample size: 30
• Recruitment status: Active, not recruiting
• URL: https://anzctr.org.au/ACTRN12617000084381.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Ms Delaine Smith

• Name: Dr Shaun Fleming

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age 40 to 65 (inclusive)
2. Newly diagnosed B-precursor acute lymphoblastic leukaemia without Ph positive disease
3. CD19 positive diseases
4. Provision of informed consent for this study
5. Patient has a life-expectancy from non-leukaemia related causes ofgreater than 3 months
6. ECOG performance status of 0 to 2 inclusive
7. Absence of serious cardiac, pulmonary, hepatic or renal disease. A serum creatinine of less than 1.5 times the institutional upper limit of normal (ULN) and serum bilirubin less than 2.5 times ULN is required
8. Normal left ventricular ejection fraction, as per local institutional standards
9. No contraindication for use of study drugs

Exclusion criteria: 1. A history of major medication non-compliance
2. Evidence of known active central nervous system (CNS) leukaemia
3. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis, with the exception of history of CNS leukaemia that is controlled with intrathecal therapy
4. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
5. Pregnant or lactating
6. Women of child-bearing potential who are not willing to use 2 highly effective methods of contraception while receiving study therapy and for 3 months after completion
7. Men who are not willing to use 2 highly effective methods of contraception while receiving study therapy and for 3 months after completion
8. Men who have a pregnant partner and are not willing to use a condom while performing sexual activity or for 3 months after completion of study therapy
9. Subjects with a known sensitivity to immunoglobulins or other components of the investigational product
10. Previous diagnosis of cancer within 5 years of current diagnosis except successfully treated Basal Cell Carcinoma, Squamous Cell Carcinoma or carcinoma in situ of the cervix
11. HIV positive
12. Significant active liver disease or active Hepatitis C Virus (HCV; RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B Virus (HBV; DNA PCR-positive) infection. Only patients who are HBV surface antigen (HBVsAg) and/or HBV core antibody (HBVcAb) positive are required to undergo HBV DNA PCR testing. Subjects with PCR-negative HBV or who are HBV core antibody positive are permitted in the study but must be on HBV prophylaxis.
13. Presence of New York Heart Association stage 2 or higher cardiac symptoms not related to the disease under study
14. Significant concomitant illnesses which would in the investigator’s opinion not make the patient a good candidate for the trial
15. Any other form of known condition or behaviour that deems the patient a poor candidate
16. Subjects who have been vaccinated with live virus vaccines less than 2 weeks prior to registration.


Age minimum: 40 Years
Age maximum: 65 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Leukaemia - Acute leukaemia

newly diagnosed acute lymphoblastic leukaemia;
newly diagnosed acute lymphoblastic leukaemia

Intervention(s)

Prephase 15 day debulking therapy consisting of 10mg/m^2/day vincristine days 1-4 and days 11-14 IV or oral (at the discretion of treating oncologist), 2mg/day IV vincristine day 1 and day 11, cyclohosphamide 150mg.m^2 twice daily IV day 1 to day 3.
A cycle: Blinatumomab 28 micrograms per day continuous iv infusion for alternative 28 day cycles
B cycle: Methylprednisolone 50mg/day twice daily oral day 1 to day 3, methotrexate 200mg/m^2 IV 2 hour continuous infusion on day 1, methotrexate 800mg/m^2 IV 22 hour continuous infusion on day 1, cytarabine 3000mg/m^2/ day IV twice daily on day 2 and day 3 in alternating 28 day cycles with A cycle treatment for a total of 4 cycles of A cycles and 4 cycles of B cycles.
Maintenance therapy will be vincristine 2mg IV day 1, prednisolone 200mg/day orally days 1-5, mercaptopurine 50mg/m^2 orally for 28 days three times a day, methotrexate 20mg/m^2 orally per week on days 1, 8, 15 and 21 repeated at 28 day intervals for 24 months.

Primary Outcome(s)

Event free status. Events include death from any cause, refractory disease (failure to achieve complete response at the end of Blinatumomab cycle 2A), progressive disease, relapsed disease , off protocol for any reason (other than ASCT), or deemed lost to follow-up[ 2 years from date of registration]

Secondary Outcome(s)

Depth of response defined as achievement of minimal residual disease (MRD) negative state as assessed by quantitative real-time polymerase chain reaction assay.[ at the ends of cycles 1B, 2B and 4B]

quality of life using Fact Leu[ at the end of cycles 1B, 2B and 4B.]

Clinical response defined as achievement of complete response
Complete response determined by:
Absence of circulating blasts or extramedullary disease
No reoccurrence for 4 weeks
Absolute Neutrophil Count (ANC) >1000/microL
Platelets >100,000/microL
[ at the end of the Blinatumomab cycle 2A.]

overall survival[ after last patient completes 5 years from trial registration]

Safety- adverse events
Assessed via biochemistry, vital signs, ECG[ 30 days after last dose of blinatumomab]

cytokine release syndrome rates in induction[ completion of cycle 1B therapy]

Event free survival which includes death from any cause, refractory disease, progressive disease, relapsed disease or off protocol for any reason (other than for Allogeneic stem cell transplant). [ after last patient completes 2 years from registration]

tolerability- determined by dose intensity and the number of patients completing per protocol therapy until the end of cycle 4B.[ end of cycle 4B, end of 1st 6 cycles of maintenance therapy, end of maintenance therapy]

Secondary ID(s)

ALLG ALL8

Source(s) of Monetary Support

Australasian Leukaemia and Lymphoma Group

Ethics review

Status: Approved
Approval date: 22/12/2017
Contact:

Alfred Hospital HREC

Results

• Date Posted: 07/06/2022