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Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL) (REMoDL-A)

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
R-CHOP
R-CHOP + acalabrutinib
Sponsored by
University Hospital Southampton NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring Lymphoma, Acalabrutinib, R-CHOP, DLBCL, Non Hodgkin Lymphoma, Haematological cancer, Bruton Tyrosine Kinase, Molecular Profiling, Chemoimmunotherapy

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material must be available to forward to HMDS for gene expression profiling and central pathology review. The following diagnoses by 2016 WHO classification of lymphoid neoplasms may be included:

    • DLBCL, not otherwise specified (NOS)
    • T-cell/histiocyte-rich large B-cell lymphoma
    • Epstein-Barr virus positive DLBCL, NOS
    • ALK-positive large B-cell lymphoma
    • HHV8-positive DLBCL, NOS
    • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma)
    • High-grade B-cell lymphoma, NOS
  • At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT.
  • Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent.
  • Stage IAX (bulk defined as lymph node mass [either single or conglomerate] diameter >7.5cm) to stage IV disease and deemed to require a full course of chemotherapy. Patients with non-bulky IE disease will not be eligible.
  • ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma.
  • Adequate bone marrow function with platelets > 100x109/L; neutrophils > 1.0x109/L at study entry, unless lower figures are attributable to lymphoma.
  • Measured or calculated creatinine clearance > 30mls/min, (calculated using the formula of Cockcroft and Gault [(140-Age) x Mass (kg) x (1.04 (for women) or 1.23 (for men))/Serum Creatinine (μmolL)]).
  • Serum bilirubin < 35μmol/L and transaminases < 1.5x upper limit of normal at time of study entry.
  • Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram or MUGA is required to establish baseline LVEF equal to or greater than institutional normal range.
  • No concurrent uncontrolled medical condition.
  • Life expectancy > 3 months.
  • Aged 16 years or above.
  • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent.

Exclusion Criteria:

  • Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.
  • Patients who have received immunisation with a live vaccine within four weeks prior to enrolment will be ineligible.
  • Diagnosis of primary mediastinal lymphoma.
  • Diagnosis of primary Central Nervous System lymphoma or secondary CNS involvement. Those patients presenting with neurological symptoms should be investigated for CNS involvement. Routine CNS imaging or diagnostic lumbar puncture will not be required in the absence of symptoms.
  • History of stroke or intracranial haemorrhage in preceding 6 months.
  • History of bleeding diathesis (eg, haemophilia, von Willebrand disease).
  • History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components).
  • Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon) within 7 days of first dose of acalabrutinib. However patients using therapeutic low molecule weight heparin or low dose aspirin will be eligible as will those receiving direct oral anticoagulants.
  • Prior exposure to an inhibitor in the BCR pathway (eg, Btk inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (eg, ABT-199).
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
  • Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors should switch to short-acting H2-receptor antagonists or antacids prior to the commencement of acalabrutinib, if randomised to receive acalabrutinib.
  • Active significant infection (e.g. progressive multifocal leukoencephalopathy (PML)).
  • Uncontrolled autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
  • Major surgery in the preceding 4 weeks of first dose of acalabrutinib (if applicable). If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of acalabrutinib (if applicable).
  • Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than for lymphoma symptom control. Patients receiving corticosteroid treatment with <30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisone 100 mg or equivalent could be given for a maximum of 14 days as a prephase. A dose of up to 30mg or prednisolone or equivalent may be used during the screening phase to control symptoms.
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
  • Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.

    1. Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
    2. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Women who can bear children must agree to use two highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose.
  • Breastfeeding or pregnant women.
  • Men who can father children must agree to use two highly effective forms of contraception with additional barrier or abstinence during the study and for 12 months after the last treatment dose.
  • Men must agree to refrain from sperm donation during the study and for 12 months after the last treatment dose.
  • Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent.
  • Prior malignancy (other than DLBCL), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years.
  • Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease, resection of the stomach or small bowel, partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass that would limit absorption of oral medication.
  • Any immunotherapy within 4 weeks of 1st dose of the study.
  • Concurrent participation in another therapeutic clinical trial.

Sites / Locations

  • Colchester General HospitalRecruiting
  • East Kent Hospitals NHS Foundation TrustRecruiting
  • Monklands HospitalRecruiting
  • Victoria HospitalRecruiting
  • University Hospital Dorset NHS Foundation Trust (Bournemouth and Poole Hospitals)Recruiting
  • Queens HospitalRecruiting
  • Addenbrooke's HospitalRecruiting
  • Royal Derby HospitalRecruiting
  • Royal Devon and Exeter HospitalRecruiting
  • Beatson West of Scotland Cancer CentreRecruiting
  • Ipswich HospitalRecruiting
  • St James HospitalRecruiting
  • Leicester Royal InfirmaryRecruiting
  • Chase Farm and Barnet HospitalsRecruiting
  • Lewisham and Greenwich NHS TrustRecruiting
  • University College London HospitalRecruiting
  • Maidstone HospitalRecruiting
  • The Christie HospitalRecruiting
  • Milton Keynes University HospitalRecruiting
  • Freeman HospitalRecruiting
  • Norfolk and Norwich University HospitalRecruiting
  • Nottingham City HospitalRecruiting
  • Royal Oldham HospitalRecruiting
  • Churchill HospitalRecruiting
  • Derriford HospitalRecruiting
  • Queen Alexandra HospitalRecruiting
  • Queen's HospitalRecruiting
  • Southampton General HospitalRecruiting
  • Royal Stoke University HospitalRecruiting
  • Singleton HospitalRecruiting
  • Torbay HospitalRecruiting
  • Royal Cornwall HospitalRecruiting
  • Worthing and St Richards HospitalsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A Control

Arm B Experimental

Arm Description

6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy every 21 days.

1 cycle of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy followed by 5 cycles of R-CHOP + acalabrutinib taken twice daily for 21 day cycles.

Outcomes

Primary Outcome Measures

To establish if combining acalabrutinib with R-CHOP improves efficacy, compared to RCHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.
Progression-free survival (PFS) is defined as time from registration to progression/death from any cause.

Secondary Outcome Measures

To compare PFS between molecular groups.
PFS interaction with cell of origin phenotype (ABC, GCB and unclassifiable).
To compare PFS between treatment groups.
PFS interaction with clinical variables, including for example IPI, bulk, components of IPI, age and others to be determined in the SAP.
To compare overall survival (OS) between both treatment and molecular groups.
Overall survival (OS), defined as time from registration to death from any cause.
To compare event free survival (EFS) between both treatment and molecular groups.
Event-free survival (EFS), or time to treatment failure, defined as time from registration to any treatment failure including disease progression, or discontinuation of treatment for any reason.
To compare disease free survival (DFS) between both treatment and molecular groups.
Disease-free survival (DFS), defined as time of documentation of disease-free state to disease recurrence or death as a result of lymphoma or acute toxicity of treatment.
To compare time to progression (TTP) between both treatment and molecular groups.
Time to progression (TTP), defined as time from registration until documented lymphoma progression or death as a result of lymphoma. Deaths from other causes are censored at the time of death.
To compare duration of response (DoR) between both treatment and molecular groups.
Response duration (DoR), defined as the time from documentation of response until the documentation of relapse or progression.
To compare overall response rate (ORR) and complete response rate (CR) between both treatment groups.
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
To assess differences in toxicity between assigned treatments.
Evaluation of toxicity according to CTCAE version 5.
To assess differences in quality of life between treatment arms.
Application of the EORTC QLQ-C30 and FACT-Lym questionnaires.

Full Information

First Posted
August 11, 2020
Last Updated
October 25, 2022
Sponsor
University Hospital Southampton NHS Foundation Trust
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04546620
Brief Title
Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)
Acronym
REMoDL-A
Official Title
A Randomised Phase II Evaluation of Molecular Guided Therapy for Diffuse Large B-Cell Lymphoma With Acalabrutinib
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2021 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Southampton NHS Foundation Trust
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study evaluates the addition of Acalabrutinib to current standard therapy of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) for patients with previously untreated CD20 positive Diffuse Large B-cell Lymphoma (DLBCL) requiring full course chemoimmunotherapy. All patients will receive one cycle of R-CHOP. Two thirds of patients (Arm B) will go on to receive a further 5 cycles (every 21 days) of R-CHOP with Acalabrutinib. Acalabrutinib will be taken orally twice daily continuously in 21 day cycles. One third of patients (Arm A) will continue with 5 cycles of R-CHOP. Patients will be followed up initially for 24 months and then for disease status and survival until 114 progression events have been observed.
Detailed Description
Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin's lymphomas. Whilst the majority of patients will respond well to conventional treatment (R-CHOP - rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), a significant number of patients lymphoma will not respond to initial therapy or their disease will return after completion of therapy. In a number of B-cell diseases an enzyme called, Bruton tyrosine kinase (BTK) prevents death of tumour cells, including in DLBCL. Acalabrutinib is an orally active BTK-inhibitor and it is thought that stopping BTK being activated may help in treating B-cell diseases. It is hypothesised that the addition of Acalabrutinib to standard R-CHOP immunochemotherapy may improve outcomes of patients with DLBCL. REMoDL-A is a randomised, phase II, open label, multicentre study that will be open in up to 50 centres. Up to 553 patients (453 randomised) will be recruited. Following informed consent all patients will receive 1 cycle of conventional R-CHOP chemotherapy. At the same time the diagnostic pathology block will be sent for molecular profiling by the Haematological Malignancy Diagnostic Service (HMDS). The delivery of the first cycle of R-CHOP will allow a sufficient interval for real time determination of molecular phenotype. Patients whose biopsies yield sufficient tumour material for profiling will be randomised 2:1 in favour of the experimental arm (R-CHOP + acalabrutinib). The primary objective will be to establish if combining acalabrutinib with R-CHOP improves efficacy, compared to R-CHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
Lymphoma, Acalabrutinib, R-CHOP, DLBCL, Non Hodgkin Lymphoma, Haematological cancer, Bruton Tyrosine Kinase, Molecular Profiling, Chemoimmunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
453 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A Control
Arm Type
Active Comparator
Arm Description
6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy every 21 days.
Arm Title
Arm B Experimental
Arm Type
Experimental
Arm Description
1 cycle of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy followed by 5 cycles of R-CHOP + acalabrutinib taken twice daily for 21 day cycles.
Intervention Type
Drug
Intervention Name(s)
R-CHOP
Other Intervention Name(s)
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone
Intervention Description
Arm A patients will receive R-CHOP alone.
Intervention Type
Drug
Intervention Name(s)
R-CHOP + acalabrutinib
Other Intervention Name(s)
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone, Acalabrutinib
Intervention Description
Arm B patients will receive R-CHOP in combination with acalabrutinib.
Primary Outcome Measure Information:
Title
To establish if combining acalabrutinib with R-CHOP improves efficacy, compared to RCHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.
Description
Progression-free survival (PFS) is defined as time from registration to progression/death from any cause.
Time Frame
Last patient's last follow up, approximately 4.5 years. Patients who do not experience a PFS event will be censored at the date of last follow up.
Secondary Outcome Measure Information:
Title
To compare PFS between molecular groups.
Description
PFS interaction with cell of origin phenotype (ABC, GCB and unclassifiable).
Time Frame
Last patient's last follow-up, approximately 4.5 years.
Title
To compare PFS between treatment groups.
Description
PFS interaction with clinical variables, including for example IPI, bulk, components of IPI, age and others to be determined in the SAP.
Time Frame
Last patient's last follow-up, approximately 4.5 years.
Title
To compare overall survival (OS) between both treatment and molecular groups.
Description
Overall survival (OS), defined as time from registration to death from any cause.
Time Frame
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience an OS event will be censored at the date of last follow-up.
Title
To compare event free survival (EFS) between both treatment and molecular groups.
Description
Event-free survival (EFS), or time to treatment failure, defined as time from registration to any treatment failure including disease progression, or discontinuation of treatment for any reason.
Time Frame
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience an EFS event will be censored at the date of last follow-up.
Title
To compare disease free survival (DFS) between both treatment and molecular groups.
Description
Disease-free survival (DFS), defined as time of documentation of disease-free state to disease recurrence or death as a result of lymphoma or acute toxicity of treatment.
Time Frame
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a DFS event will be censored at the date of last follow-up.
Title
To compare time to progression (TTP) between both treatment and molecular groups.
Description
Time to progression (TTP), defined as time from registration until documented lymphoma progression or death as a result of lymphoma. Deaths from other causes are censored at the time of death.
Time Frame
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a TTP event will be censored at the date of last follow-up.
Title
To compare duration of response (DoR) between both treatment and molecular groups.
Description
Response duration (DoR), defined as the time from documentation of response until the documentation of relapse or progression.
Time Frame
Last patient's last follow-up, approximately 4.5 years. Patients who do not experience a RD event will be censored at the date of last follow-up.
Title
To compare overall response rate (ORR) and complete response rate (CR) between both treatment groups.
Description
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
Time Frame
Complete and overall response rates, as recorded at the end of treatment (up to 21 weeks) .
Title
To assess differences in toxicity between assigned treatments.
Description
Evaluation of toxicity according to CTCAE version 5.
Time Frame
At all visits up to 24 months follow-up.
Title
To assess differences in quality of life between treatment arms.
Description
Application of the EORTC QLQ-C30 and FACT-Lym questionnaires.
Time Frame
At baseline, cycle 2 day 1, cycle 3 day 1, cycle 5 day 1, end of treatment and at 3, 6, 12, 20 and 24 month follow-ups. Each cycle is 21 days.
Other Pre-specified Outcome Measures:
Title
To explore correlation of molecular characteristics in tumour material to clinical outcomes.
Description
Applying the following techniques to FFPE tumour material: mutational panel, FISH analysis, immunohistochemical analysis for dual protein expression of Myc and Bcl2 and dynamic changes in ctDNA and methylation based ctDNA during treatment and follow up.
Time Frame
At baseline, cycle 2 day 1, cycle 3 day 1, end of treatment and at 3, 6, 9 and 12 month follow-ups. Each cycle is 21 days.
Title
To explore correlation of baseline PET features including tumour burden and bone marrow involvement to clinical outcomes.
Description
Tumour burden defined by metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG). Bone marrow involvement defined by focal uptake in the bone marrow higher than liver uptake; diffuse bone marrow uptake higher than liver uptake will be recorded and correlated with bone marrow biopsy results where available (number and location of extranodal sites).
Time Frame
Baseline and end of treatment (up to 21 weeks).
Title
To explore combination(s) of clinical risk factors, molecular characteristics and PET features to clinical outcomes.
Time Frame
Baseline and end of treatment (up to 21 weeks).
Title
To compare metabolic response between molecular groups.
Time Frame
Baseline and end of treatment (up to 21 weeks).
Title
To update existing metabolic response criteria using advanced PET reconstructions.
Time Frame
Baseline and end of treatment (up to 21 weeks).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material must be available to forward to HMDS for gene expression profiling and central pathology review. The following diagnoses by 2016 WHO classification of lymphoid neoplasms may be included: DLBCL, not otherwise specified (NOS) T-cell/histiocyte-rich large B-cell lymphoma Epstein-Barr virus positive DLBCL, NOS ALK-positive large B-cell lymphoma HHV8-positive DLBCL, NOS High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) High-grade B-cell lymphoma, NOS At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT. Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent. Stage IAX (bulk defined as lymph node mass [either single or conglomerate] diameter >7.5cm) to stage IV disease and deemed to require a full course of chemotherapy. Patients with non-bulky IE disease will not be eligible. ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma. Adequate bone marrow function with platelets > 100x109/L; neutrophils > 1.0x109/L at study entry, unless lower figures are attributable to lymphoma. Measured or calculated creatinine clearance > 30mls/min, (calculated using the formula of Cockcroft and Gault [(140-Age) x Mass (kg) x (1.04 (for women) or 1.23 (for men))/Serum Creatinine (μmolL)]). Serum bilirubin < 35μmol/L and transaminases < 1.5x upper limit of normal at time of study entry. Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram or MUGA is required to establish baseline LVEF equal to or greater than institutional normal range. No concurrent uncontrolled medical condition. Life expectancy > 3 months. Aged 16 years or above. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. Ability to understand the purpose and risks of the study and provide signed and dated informed consent. Exclusion Criteria: Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible. Patients who have received immunisation with a live vaccine within four weeks prior to enrolment will be ineligible. Diagnosis of primary mediastinal lymphoma. Diagnosis of primary Central Nervous System lymphoma or secondary CNS involvement. Those patients presenting with neurological symptoms should be investigated for CNS involvement. Routine CNS imaging or diagnostic lumbar puncture will not be required in the absence of symptoms. History of stroke or intracranial haemorrhage in preceding 6 months. History of bleeding diathesis (eg, haemophilia, von Willebrand disease). History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components). Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon) within 7 days of first dose of acalabrutinib. However patients using therapeutic low molecule weight heparin or low dose aspirin will be eligible as will those receiving direct oral anticoagulants. Prior exposure to an inhibitor in the BCR pathway (eg, Btk inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (eg, ABT-199). Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors should switch to short-acting H2-receptor antagonists or antacids prior to the commencement of acalabrutinib, if randomised to receive acalabrutinib. Active significant infection (e.g. progressive multifocal leukoencephalopathy (PML)). Uncontrolled autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP). Major surgery in the preceding 4 weeks of first dose of acalabrutinib (if applicable). If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of acalabrutinib (if applicable). Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than for lymphoma symptom control. Patients receiving corticosteroid treatment with <30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisone 100 mg or equivalent could be given for a maximum of 14 days as a prephase. A dose of up to 30mg or prednisolone or equivalent may be used during the screening phase to control symptoms. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy. Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Women who can bear children must agree to use two highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose. Breastfeeding or pregnant women. Men who can father children must agree to use two highly effective forms of contraception with additional barrier or abstinence during the study and for 12 months after the last treatment dose. Men must agree to refrain from sperm donation during the study and for 12 months after the last treatment dose. Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent. Prior malignancy (other than DLBCL), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 2 years. Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease, resection of the stomach or small bowel, partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass that would limit absorption of oral medication. Any immunotherapy within 4 weeks of 1st dose of the study. Concurrent participation in another therapeutic clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicole Keyworth
Phone
023 8120 3785
Email
n.e.keyworth@soton.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Joshua Caddy
Phone
023 8120 5537
Email
j.caddy@soton.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Davies
Organizational Affiliation
University of Southampton
Official's Role
Principal Investigator
Facility Information:
Facility Name
Colchester General Hospital
City
Colchester
State/Province
Essex
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
East Kent Hospitals NHS Foundation Trust
City
Canterbury
State/Province
Kent
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Monklands Hospital
City
Airdrie
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Victoria Hospital
City
Blackpool
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University Hospital Dorset NHS Foundation Trust (Bournemouth and Poole Hospitals)
City
Bournemouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Queens Hospital
City
Burton On Trent
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Derby Hospital
City
Derby
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Ipswich Hospital
City
Ipswich
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
St James Hospital
City
Leeds
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Chase Farm and Barnet Hospitals
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Lewisham and Greenwich NHS Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University College London Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Maidstone Hospital
City
Maidstone
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
The Christie Hospital
City
Manchester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Milton Keynes University Hospital
City
Milton Keynes
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Freeman Hospital
City
Newcastle
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Oldham Hospital
City
Oldham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Queen Alexandra Hospital
City
Portsmouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Queen's Hospital
City
Romford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Stoke University Hospital
City
Stoke-on-Trent
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Singleton Hospital
City
Swansea
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Torbay Hospital
City
Torquay
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Cornwall Hospital
City
Truro
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Worthing and St Richards Hospitals
City
Worthing
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)

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