ANZCTR - Registration

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12617000084381

Ethics application status

Approved

Date submitted

7/01/2017

Date registered

16/01/2017

Date last updated

7/04/2024

Date data sharing statement initially provided

11/06/2019

Type of registration

Prospectively registered

Titles & IDs

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

Secondary ID [1]

ALLG ALL8

Universal Trial Number (UTN)

Trial acronym

BLAM

Linked study record

Health condition

Health condition(s) or problem(s) studied:

newly diagnosed acute lymphoblastic leukaemia

Condition category

Condition code

Cancer

Leukaemia - Acute leukaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

single arm study

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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

Timepoint [1]

2 years from date of registration

Secondary outcome [1]

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).

Timepoint [1]

after last patient completes 2 years from registration

Secondary outcome [2]

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

Timepoint [2]

at the end of the Blinatumomab cycle 2A.

Secondary outcome [3]

overall survival

Timepoint [3]

after last patient completes 5 years from trial registration

Secondary outcome [4]

tolerability- determined by dose intensity and the number of patients completing per protocol therapy until the end of cycle 4B.

Timepoint [4]

end of cycle 4B, end of 1st 6 cycles of maintenance therapy, end of maintenance therapy

Secondary outcome [5]

Safety- adverse events
Assessed via biochemistry, vital signs, ECG

Timepoint [5]

30 days after last dose of blinatumomab

Secondary outcome [6]

cytokine release syndrome rates in induction

Timepoint [6]

completion of cycle 1B therapy

Secondary outcome [7]

Depth of response defined as achievement of minimal residual disease (MRD) negative state as assessed by quantitative real-time polymerase chain reaction assay.

Timepoint [7]

at the ends of cycles 1B, 2B and 4B

Secondary outcome [8]

quality of life using Fact Leu

Timepoint [8]

at the end of cycles 1B, 2B and 4B.

Eligibility

Key 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

Minimum age

40 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

single arm trial

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

trial is a proof of concept trial.An observed event-free rate of 63% at 2 years is deemed to be an important signal. The lower clinical threshold for futility will be set at 50% at 2 years.
Using the Neuenschwander Proof of Concept (PoC) approach the criteria for PoC will be set to;
An observed event-free rate at 2 years of =63%
Posterior probability that the true rate exceeds 50% is >90% (given observed data)

It could be described as the “Bayesian power” in this context and if the true rate is > 67%, a sample size of 60 is a justifiable upper limit on the sample size; with higher, true event-free rates the probability that both PoC criteria are met exceeds 80% at substantially smaller sample sizes. With a sample size of 30 there is a reasonable probability (>80%) of meeting the PoC criteria for the primary endpoint when the true event-free rate at 2 years is 70% or more. The probability that the PoC criteria will be met when the true rate is 50% or less, is 10% or less when more than 25 patients have been assessed.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

16/04/2018

Actual

17/05/2018

Date of last participant enrolment

Anticipated

20/12/2020

Actual

29/09/2020

Date of last data collection

Anticipated

3/07/2025

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment hospital [2]

Box Hill Hospital - Box Hill

Recruitment hospital [3]

The Canberra Hospital - Garran

Recruitment hospital [4]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [5]

Royal North Shore Hospital - St Leonards

Recruitment hospital [6]

Royal Perth Hospital - Perth

Recruitment hospital [7]

St Vincent's Hospital (Darlinghurst) - Darlinghurst

Recruitment hospital [8]

Westmead Hospital - Westmead

Recruitment hospital [9]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [10]

Peter MacCallum Cancer Centre - Melbourne

Recruitment postcode(s) [1]

2010 - Darlinghurst

Recruitment postcode(s) [2]

2065 - St Leonards

Recruitment postcode(s) [3]

2145 - Westmead

Recruitment postcode(s) [4]

2605 - Garran

Recruitment postcode(s) [5]

3000 - Melbourne

Recruitment postcode(s) [6]

3004 - Prahran

Recruitment postcode(s) [7]

3128 - Box Hill

Recruitment postcode(s) [8]

4029 - Herston

Recruitment postcode(s) [9]

5000 - Adelaide

Recruitment postcode(s) [10]

6000 - Perth

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Australasian Leukaemia and Lymphoma Group

Address [1]

35 Elizabeth St, Richmond, VIC 3121

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Australasian Leukaemia and Lymphoma Group

Address

35 Elizabeth St, Richmond, VIC 3121

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital HREC

Ethics committee address [1]

55 Commercial Road, Melbourne, VIC, 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

13/11/2017

Approval date [1]

22/12/2017

Ethics approval number [1]

HREC/17/Alfred/200

Summary

Brief 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.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Shaun Fleming

Address

The Alfred Hospital
55 Commercial Road, Prahran, VIC 3004

Country

Australia

Phone

+61 3 9076 2000

Fax

S.Fleming2@alfred.org.au

Contact person for public queries

Name

Delaine Smith

Address

Australasian Leukaemia and Lymphoma Group Ground floor, 35 Elizabeth St, Richmond, VIC 3121

Country

Australia

Phone

+61 3 8373 9701

Fax

delaine.smith@allg.org.au

Contact person for scientific queries

Name

Shaun Fleming

Address

The Alfred Hospital
55 Commercial Road, Prahran, VIC 3004

Country

Australia

Phone

+61 3 9076 2000

Fax

S.Fleming2@alfred.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified IPD data for all data collected during the trial

When will data be available (start and end dates)?

Data available 3 months following publication, for an indefinite period

Available to whom?

Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.

Available for what types of analyses?

Any type of analysis
Assessed on a case-by-case basis

How or where can data be obtained?

Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to info@allg.org.au

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
22126	Study protocol			info@allg.org.au	Access can be requested via the Health Data Austra... [More Details]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy	2020	https://doi.org/10.2147/blctt.s223894
Dimensions AI	Targeted Therapy in Acute Lymphoblastic Leukaemia	2021	https://doi.org/10.3390/jpm11080715

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Did you know?

Documents added manually

Documents added automatically