ActivePhase 2ACTRN12617000084381

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

Sponsor

Australasian Leukaemia and Lymphoma Group

Enrollment

30 participants

Start Date

May 17, 2018

Study Type

Interventional

Conditions

newly diagnosed acute lymphoblastic leukaemia

Summary

The primary purpose of this trial is to evaluate the safety and efficacy of a Blinatumomab, Cytarabine (AraC) and Methotrexate therapy protocol for the treatment of acute lymphoblastic leukaemia. Who is it for? You may be eligible to enroll in this trial if you are aged 40 to 65 years, and have been newly diagnosed with B-precursor acute lymphoblastic leukaemia without Ph positive disease. Study details All participants enrolled in this trial will receive the same therapy protocol. This involves a 15-day debulking treatment with oral and/or intravenous vincristine followed by eight 28-day cycles alternating between intravenous blinatumomab therapy and intravenous methotrexate, methylprednisolone and cytarabine. After completing these alternating cycles, maintenance treatment will continue in 28-day cycles for 24 months with a combination of intravenous vincristine and oral prednisolone, mercaptopurine and methotrexate. Participants will be asked to complete questionnaires regarding their quality of life and will undergo assessments for disease progression, side effects and survival for 5 years.

Eligibility

Sex: Both males and femalesMin Age: 40 YearssMax Age: 65 Yearss

Inclusion Criteria9

Age 40 to 65 (inclusive)
Newly diagnosed B-precursor acute lymphoblastic leukaemia without Ph positive disease
CD19 positive diseases
Provision of informed consent for this study
Patient has a life-expectancy from non-leukaemia related causes ofgreater than 3 months
ECOG performance status of 0 to 2 inclusive
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
Normal left ventricular ejection fraction, as per local institutional standards
No contraindication for use of study drugs

Exclusion Criteria16

A history of major medication non-compliance
Evidence of known active central nervous system (CNS) leukaemia
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
Current autoimmune disease or history of autoimmune disease with potential CNS involvement
Pregnant or lactating
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
Men who are not willing to use 2 highly effective methods of contraception while receiving study therapy and for 3 months after completion
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
Subjects with a known sensitivity to immunoglobulins or other components of the investigational product
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
HIV positive
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.
Presence of New York Heart Association stage 2 or higher cardiac symptoms not related to the disease under study
Significant concomitant illnesses which would in the investigator’s opinion not make the patient a good candidate for the trial
Any other form of known condition or behaviour that deems the patient a poor candidate
Subjects who have been vaccinated with live virus vaccines less than 2 weeks prior to registration.

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Interventions

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.