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Trial registered on ANZCTR


Registration number
ACTRN12619000990123
Ethics application status
Approved
Date submitted
29/03/2019
Date registered
11/07/2019
Date last updated
19/03/2021
Date data sharing statement initially provided
11/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to look at the safety and efficacy of Acalabrutinib and Rituximab followed by chemo with or without Autologous stem cell transplant (ASCT) and maintenance Acalabrutinib and Rituximab in fit patients with previously untreated mantle cell lymphoma.
Scientific title
An ALLG Window study of Acalbrutinib plus Rituximab followed by R-DHAOx+ASCT in fit Mantle Cell Lymphoma.
Secondary ID [1] 297845 0
NHL33
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle cell Lymphoma 312218 0
Condition category
Condition code
Cancer 310762 310762 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive:
Induction phase: (Acalabrutinib + Rituximab 2 cycles every 4 weeks, cycle = 28 days)
Rituximab 375mg/m2 Intravenously D1
Acalabrutinib 100mg orally, twice a day, D1-D28

Followed by:
Chemotherapy phase: R-DHAOx 4 cycles every 21 days

Rituximab 375 mg/m2 Intravenously on day 1
Dexamethasone 40 mg Intravenously or Orally (tablets) on days 1 to 4 (the mode of administration is based on local site practice and availability)
Cytarabine 2000 mg/m2 Intravenously every 12 h on day 2
Oxaliplatin 100 mg/m² Intravenously on day 1.

IF response to R-DHAOx is less than a partial response the patient will be taken off study and treated as per local guidelines. The response will be determined by review of a PET/CT scan taken after the patient has completed 4 cycles of R-DHAOx.

IF response to R-DHAOx is greater than or equal to a partial response proceed to:

Consolidation phase:
BEAM Autologous stem cell transplant

Carmustine 300 mg/m2 Intravenously on day -6
Etoposide 200 mg/m2 Intravenously on days -5 to -2
Cytarabine 200mg/m2 Intravenously TWICE a day on days -5 to -2
Melphalan 140 mg/m2 Intravenously on day -1
Peripheral stem cells injected on day 0 - dose to be determined on day by physician.

Followed by:
Maintenance phase:
All patients with a documented response at end of the chemotherapy phase will continue with 1-year of Acalabrutinib 100mg orally, twice a day continuous, and 2 years of Rituximab 375mg/m2 Intravenously every 3 months for 8 doses

Patients will be given patient diaries to monitor adherence to treatment.
Intervention code [1] 314082 0
Treatment: Drugs
Intervention code [2] 314672 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319613 0
Complete metabolic response rate
Response will be assessed in accordance with the 2014 Lugano Response assessment for Non-Hodgkin’s Lymphoma by review of PET/CT Scan.
Timepoint [1] 319613 0
To be measured after Acalabrutinib + Rituximab induction followed by R-DHAOx chemotherapy. Approximately 6 months post commencement of treatment.
Secondary outcome [1] 368857 0
Change in Response rate (Overall Response Rate (ORR), CMR, Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), relapse after CR)
Response will be assessed in accordance with the 2014 Lugano Response assessment for Non-Hodgkin’s Lymphoma by PET/CT scan. This is a composite secondary endpoint.
Timepoint [1] 368857 0
To be measured after Acalabrutinib + Rituximab, R-DHAOx chemotherapy, ASCT, end of Acalabrutinib + Rituximab maintenance and the end of Rituximab maintenance. Approximately 3 years post commencement of treatment.
Secondary outcome [2] 368858 0
Overall treatment toxicity as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
Timepoint [2] 368858 0
Any adverse event will be captured throughout treatment. This will be assessed weekly from commencement of treatment to 30 days post end of treatment.
Secondary outcome [3] 368859 0
Progression free survival (PFS) data will be collected from patients medical records.
Timepoint [3] 368859 0
This will be measured from the date of study entry to the date of first appearance of disease progression, relapse, and death from any cause; patients alive without progression or relapse will be censored at date last known to be alive. This will be assessed up to 3 years post end of treatment.
Secondary outcome [4] 368860 0
Overall survival.
The will be collected by reviewing patient notes and contacting the patient.
Timepoint [4] 368860 0
This will be measured at 3 years after study entry.

Eligibility
Key inclusion criteria
1. Age 18 – 70 years
2. Histologically confirmed diagnosis of CD20 positive mantle cell lymphoma (MCL)
3. No prior lymphoma treatment including chemotherapy, radiotherapy or other investigational drug
4. Stage II-IV disease by Ann Arbor Criteria. Patients with stage I disease with bulk (greater than 7cms) that require systemic treatment will also be eligible. (must be able to undergo PET/CT imaging for staging purposes).
5. PET/CT avid disease at baseline.
6. Eastern Collaborative Oncology Group (ECOG) performance status 0, or 1, unless attributable to lymphoma in which case patients of performance status 2 are also eligible.
7. Adequate bone marrow function with haemoglobin greater than 80g/L, neutrophils greater than 1.0x109/L and platelets greater than 80x109/L at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
8. Adequate renal function defined by an estimated creatinine clearance greater than or equal to 40 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
9. Adequate hepatic function defined by a total bilirubin level less than or equal to 2 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels less than or equal to 3 × upper limit of institutional normal range unless attributed to lymphoma or Gilbert’s syndrome.
10. Patients must have an acceptable left ventricular ejection fraction (LVEF) i.e. within the local normal range for gated heart pool scan or echocardiogram
11. Life expectancy greater than 3 months.
12. Negative blood pregnancy test at screening for women of childbearing potential.
13. Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any lymphoma not fulfilling the WHO diagnostic criteria1 for mantle cell lymphoma
2. Central nervous system involvement including meningeal involvement or cord compression from lymphoma
3. Subjects aged less than 18 or more than 70 years at screening
4. Subjects that are deemed not suitable for autologous stem cell transplant, in the opinion of the treating physician, at time of screening.
5. Subjects with a contraindication to study treatments
6. Prior organ transplantation, including allogeneic stem-cell transplantation
7. Prior malignancy, active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
8. Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
9. Past history of interstitial lung disease.
10. Any other serious active disease
11. Presence of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Only patients who are HBV surface antigen (HBVsAg) and/or HBV core antibody (HBVcAb) positive are required to undergo HBV DNA PCR testing. Subjects that are HBV DNA negative who are HBVcAb positive are permitted in the study but must be on HBV prophylaxis.
12. Live vaccines within 30 days prior to the first dose of study drug and while participating in the study.
13. Uncontrolled AIHA (autoimmune hemolytic anaemia) or ITP (idiopathic thrombocytopenia pupura).
14. Suspicion of or confirmed progressive multifocal leukoencephalopathy
15. Has difficulty with or is unable to swallow oral medication, or significant gastrointestinal disease that would limit absorption of oral medication
16. Pregnant or lactating

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 18951 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 18952 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 18953 0
Gold Coast University Hospital - Southport
Recruitment hospital [4] 18954 0
The Townsville Hospital - Douglas
Recruitment hospital [5] 18955 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [6] 18956 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 18957 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 18958 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 33458 0
3084 - Heidelberg
Recruitment postcode(s) [2] 33459 0
2139 - Concord
Recruitment postcode(s) [3] 33460 0
4215 - Southport
Recruitment postcode(s) [4] 33461 0
4814 - Douglas
Recruitment postcode(s) [5] 33462 0
2010 - Darlinghurst
Recruitment postcode(s) [6] 33463 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 33464 0
5042 - Bedford Park
Recruitment postcode(s) [8] 33465 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 21377 0
New Zealand
State/province [1] 21377 0

Funding & Sponsors
Funding source category [1] 302366 0
Commercial sector/Industry
Name [1] 302366 0
Acerta
Address [1] 302366 0
Acerta
121 Oyster Point Blvd,
San Francisco
CA 94080
Country [1] 302366 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Australaisn Leukeamia and Lymphoma Group
Address
ALLG
35 Elizabth Street
Richmond
Vic
3121
Country
Australia
Secondary sponsor category [1] 302254 0
None
Name [1] 302254 0
Address [1] 302254 0
Country [1] 302254 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303042 0
Austin Heath: Ethics and Research Governance
Ethics committee address [1] 303042 0
Ethics and Research Governance Unit
Level 8, Harold Stokes Building
Austin Health
PO Box 5555
Heidelberg
Victoria
3084
Ethics committee country [1] 303042 0
Australia
Date submitted for ethics approval [1] 303042 0
29/01/2020
Approval date [1] 303042 0
26/05/2020
Ethics approval number [1] 303042 0

Summary
Brief summary
This purpose of this study to evaluate the efficacy and safety of Acalabrutinib and Rituximab followed by R-DHAOx chemo with or without ASCT and maintenance Aacalabrutinib and Rituximab in fit patients with previously untreated mantle cell lymphoma.

Who is it for?

You may be eligible for this study if you are an adult who has been diagnosed with positive mantle cell lymphoma.

Study details

All participants in this study will receive the following:
1. Induction phase: one day of Rituximab in the vein and 28 days Acalabrutinib orally for 2 cycles.
2. Chemotherapy phase: 4 cycles of chemotherapy (21 day cycles)
3. Consolidation phase: including stem cell transplant
4. Maintenance phase: Acalabrutinib orally for one year and Rituximab in the vein every 3 months for 2 years.

During the trial patients will have blood tests performed and undergo up to 5 PET/CT scans to help determined the progress of the treatment.

It is hoped that this research will help determine whether this treatment is safe for patients, and what kinds of side effects/complications may occur with this treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92262 0
Dr Eliza Hawkes
Address 92262 0
Level 4
ONJCWC
145 Studley rd
Heidelberg
Vic 3084
Country 92262 0
Australia
Phone 92262 0
+61 3 9496 5763
Fax 92262 0
Email 92262 0
Eliza.Hawkes@onjcri.org.au
Contact person for public queries
Name 92263 0
Ms Delaine Smith
Address 92263 0
ALLG
35 Elizabeth street
Richmond
Vic
3121
Country 92263 0
Australia
Phone 92263 0
+61 3 8373 9701
Fax 92263 0
Email 92263 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 92264 0
Ms Delaine Smith
Address 92264 0
ALLG
35 Elizabeth street
Richmond
Vic
3121
Country 92264 0
Australia
Phone 92264 0
+61 3 8373 9701
Fax 92264 0
Email 92264 0
delaine.smith@allg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publically. Aggregate patient data and final results will be presented in the final report
What supporting documents are/will be available?
No other documents available
Summary results
No Results