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Trial record 3 of 50 for:    acalabrutinib

A Combination of Acalabrutinib With R-CHOP for Patient Diffuse Large B-cell Lymphoma (DLBCL) (ACCEPT)

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ClinicalTrials.gov Identifier: NCT03571308
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Brief Summary:
Previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL) requiring full course chemoimmunotherapy.

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma Drug: R-CHOP + acalabrutinib Phase 1 Phase 2

Detailed Description:
Open-label non-randomised phase Ib/II study conducted in two stages. Stage 1 will be dose escalation in a modified classical 6+6 design. Stage 2 will be an expansion cohort to gain additional information on safety and efficacy at the recommended phase II dose of acalabrutinib.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:

A multicentre open-label non-randomised phase Ib/II two stage trial. Stage 1 - dose escalation will proceed until a maximum tolerated dose (MTD) is defined or the maximal administered dose (MAD) is determined in order to define the recommended Phase II dose (RP2D). 6 - 24 patients. Stage 2 - expansion to gain additional information on safety and efficacy at the RP2D from a total of 15 patients recruited.

Patients will receive conventionally dosed R-CHOP chemotherapy for 6 cycles with acalabrutinib introduced on cycle 2 onwards, at a dosage according to cohort number. This will allow for both clarity in the toxicity profile of the combination and also assess the impact of acalabrutinib on ADCC.

patients who do not complete six cycles of treatment for reasons other than toxicity will be replaced.

Primary Purpose: Treatment
Official Title: A Phase Ib/II Combination of Acalabrutinib With R-CHOP for Patient Diffuse Large B-cell Lymphoma (DLBCL)
Actual Study Start Date : June 2, 2017
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: R-CHOP + Acalabrutinib

Open-label non-randomised phase Ib/II study conducted in two stages. Phase I will see two doses of acalabrutinib tested. R-CHOP + acalabrutinib will be given for 6 cycles on a 21 day cycle and then two cycles of acalabrutinib only for a total of 56 days. Acalabrutinib will be introduced at Cycle 2.

Phase II will see the recommended phase 2 dose used on the same treatment regimen.

Drug: R-CHOP + acalabrutinib
Patient will be given R-CHOP and acalabrutinib
Other Names:
  • Rituximab
  • Cyclophosphamide
  • Vincristine
  • Doxorubicin
  • Prednisolone
  • Acalabrutinib




Primary Outcome Measures :
  1. Phase I: Dose limiting toxicity of acalabrutinib combined to R-CHOP [ Time Frame: 18 months ]
    Define recommended dose for Phase II evaluation of acalabrutinib with R-CHOP examining safety and toxicity of combination

  2. Phase II: Overall response rate of the combination acalabrutinib and R-CHOP [ Time Frame: 36 months ]
    Document anti-tumour activity of acalabrutinb in combination wit R-CHOP in patients with previously untreated CD20 positive DLBCL

  3. Safety of the combination acalabrutinib and R-CHOP as determined by treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: 12 months ]
    To determine additional safety information of acalabrutinib in combination with R-CHOP by treatment-related adverse events as assessed by CTCAE v4.03.


Secondary Outcome Measures :
  1. Pharmacokinetics of acalabrutinib using area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 months ]
    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

  2. Maximum Plasma Concentration (Cmax) of acalabrutinib [ Time Frame: 24 months ]
    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCLPK parameter.

  3. Time after administration when maximum concentration of acalabrutinib in the plasma is reached (Tmax) [ Time Frame: 24 months ]
    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

  4. Time required for concentration of acalabrutinib to reach half original value (T1/2) [ Time Frame: 24 months ]
    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

  5. Overall response rate of the combination acalabrutinib and R-CHOP according to cell of origin. [ Time Frame: 24 months ]
    To evaluate the effect of acalabrutinib in combination with R-CHOP on outcomes according to cell of origin

  6. Two years progression-free survival [ Time Frame: 24 months ]
    To measure the duration of response to acalabrutinib in combination with R-CHOP over a follow-up period of 2 years

  7. Two years overall survival [ Time Frame: 24 months ]
    To measure the duration of response to acalabrutinib in combination with R-CHOP over a follow-up period of 2 years



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review.
  • Measurable disease of at least 15mm.
  • Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent.
  • Stage IAX (bulk defined as lymph node diameter >10cm) 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 < 2.5x 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 55%.
  • 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:

Patients will be excluded from the study entry if any of the following criteria are met:

  • 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.
  • History of stroke or intracranial haemorrhage in preceding 6 months.
  • History of bleeding diathesis (eg, haemophilia, von Willebrand disease).
  • 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.
  • Prior exposure to a BCR inhibitor (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 who switch to short-acting H2-receptor antagonists or antacids are eligible for enrolment into this study.
  • Uncontrolled systemic infection.
  • Major surgery in the preceding 4 weeks of first dose of study drug. 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 study drug.
  • 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, or corrected QT interval (QTc) > 480 msec at screening.
  • 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.
    • Positive test results for hepatitis C (HCV antibody serology testing) will not be eligible.
  • Women who are sexually active and can bear children must agree to use highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose. Highly effective forms of contraception are defined in Section 4.7.
  • Breastfeeding or pregnant women.
  • Men who are sexually active and can father children must agree to use highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose. Highly effective forms of contraception are defined in Section 4.7.
  • 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. Note: these cases must be discussed with SCTU.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass.
  • Any immunotherapy within 4 weeks of 1st dose of the study.
  • Concurrent participation in another therapeutic clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03571308


Contacts
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Contact: Katy Mercer 0238120 ext 5154 accept@soton.ac.uk
Contact: Joshua Caddy 0238120 ext 5154 accept@soton.ac.uk

Locations
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United Kingdom
Southampton University Hospitals NHS Tust Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Kerry Gready    0238120 ext 5113    lymphomaresearcnurses@soton.ac.uk   
Contact: Julie Gwilt    0238120 ext 4202    j.gwilt@soton.ac.uk   
St James's University Hospital Not yet recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Amy Humphries    0113206 ext 8984    amyhumphries@nhs.net   
Contact: Sophie Robertson Robertson    0113206 ext 8984    sophierobertson@nhs.net   
Principal Investigator: Cathy Burton         
University College London Hospitals Not yet recruiting
London, United Kingdom, NW12PG
Contact: Tebereh Mesfin    0203 447 ext 5078    tebereh.mesfin@uclh.nhs.uk   
Contact: Jessica Rubio-Lorente    0203 4478049 ext 8049    jessica.rubio-lorente@uclh.nhs.uk   
Principal Investigator: Kirit Ardeshna         
The Christie NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M204XB
Contact: Clare Day    0161 918 ext 7516    Clare.Day@christie.nhs.uk   
Contact: Rachel Stevenson    0161 918 ext 7226    rachel.stevenson@christie.nhs.uk   
Principal Investigator: John Radford         
Nottingham City Hospital Campus Not yet recruiting
Nottingham, United Kingdom, NG51PB
Contact: Melanie Jones    0115 9691169 ext 53474    Melanie.Jones@nuh.nhs.uk   
Contact: Carol Evans    0115 9691169 ext 53474    carol.evans@nuh.nhs.uk   
Churchill Hospital Recruiting
Oxford, United Kingdom, OX37LE
Contact: Eileen McKenzie McKenzie    01865 23 ext 5312    trialadministrator02@oncology.ox.ac.uk   
Contact: Raqeeb Mahmood    01865 23 ext 5216    raqeeb.mahmood@oncology.ox.ac.uk   
Principal Investigator: Graham Collins         
Derriford Hospital Not yet recruiting
Plymouth, United Kingdom, PL68DH
Contact: Nicola Crosbie    01752 43 ext 1043    nicola.crosbie@nhs.net   
Contact: Claire Brown    01752 43 ext 9638    clairebrown10@nhs.net   
Principal Investigator: Simon Rule         
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust
Investigators
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Principal Investigator: Andy Davies Southampton University Hospital NHS Foundation Trust

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Responsible Party: University Hospital Southampton NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03571308     History of Changes
Other Study ID Numbers: RHM CAN 1129
First Posted: June 27, 2018    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Southampton NHS Foundation Trust:
Diffused Large B-Cell Lymphoma
Acalabrunitib
Bruton Tyrosine Kinase
R-CHOP
Molecular Profiling
Chemoimmunotherapy

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases