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Non Hodgkin LymphomaPhase 1/2ACCEPTNCT03571308

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

A Phase 1/2 study testing R-CHOP + acalabrutinib in people with Non Hodgkin Lymphoma, run by University Hospital Southampton NHS Foundation Trust at 7 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL) requiring full course chemoimmunotherapy. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Non Hodgkin Lymphoma
What is being tested?
R-CHOP + acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
7 sitesUnited Kingdom
Study dates
2 Jun 2017to 31 Aug 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United Kingdom7 sites

  • St James's University Hospital

    Leeds, LS9 7TF

  • University College London Hospitals

    London, NW12PG

  • The Christie NHS Foundation Trust

    Manchester, M204XB

  • Nottingham City Hospital Campus

    Nottingham, NG51PB

  • Churchill Hospital

    Oxford, OX37LE

  • Derriford Hospital

    Plymouth, PL68DH

  • Southampton University Hospitals NHS Tust

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

About this study

Official title: A Phase Ib/II Combination of Acalabrutinib With R-CHOP for Patient Diffuse Large B-cell Lymphoma (DLBCL)

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

Read the 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.

Being tested
R-CHOP + acalabrutinib
Keywords
Diffused Large B-Cell Lymphoma, Acalabrunitib, Bruton Tyrosine Kinase, R-CHOP, Molecular Profiling, Chemoimmunotherapy
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • R-CHOP + acalabrutinibDrug

    Also called Rituximab, Cyclophosphamide, Vincristine, Doxorubicin

    Patient will be given R-CHOP and acalabrutinib

Study groups in NCT03571308
Study groupRoleWhat they receive
R-CHOP + AcalabrutinibExperimentalOpen-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.
Receives: Drug: R-CHOP + acalabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Dose limiting toxicity of acalabrutinib combined to R-CHOP

    Define recommended dose for Phase II evaluation of acalabrutinib with R-CHOP examining safety and toxicity of combination

    Measured: 18 months

  2. Phase II: Overall response rate of the combination acalabrutinib and R-CHOP

    Document anti-tumour activity of acalabrutinb in combination wit R-CHOP in patients with previously untreated CD20 positive DLBCL

    Measured: 36 months

  3. Safety of the combination acalabrutinib and R-CHOP as determined by treatment-related adverse events as assessed by CTCAE v4.03.

    To determine additional safety information of acalabrutinib in combination with R-CHOP by treatment-related adverse events as assessed by CTCAE v4.03.

    Measured: 12 months

Secondary outcomes (7)

  1. Pharmacokinetics of acalabrutinib using area under the plasma concentration versus time curve (AUC)

    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

    Measured: 24 months

  2. Maximum Plasma Concentration (Cmax) of acalabrutinib

    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCLPK parameter.

    Measured: 24 months

  3. Time after administration when maximum concentration of acalabrutinib in the plasma is reached (Tmax)

    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

    Measured: 24 months

  4. Time required for concentration of acalabrutinib to reach half original value (T1/2)

    To determine the pharmacokinetic (PK) profile of acalabrutinib when given in combination with R-CHOP in patients with DLBCL

    Measured: 24 months

  5. Overall response rate of the combination acalabrutinib and R-CHOP according to cell of origin.

    To evaluate the effect of acalabrutinib in combination with R-CHOP on outcomes according to cell of origin

    Measured: 24 months

  6. Two years progression-free survival

    To measure the duration of response to acalabrutinib in combination with R-CHOP over a follow-up period of 2 years

    Measured: 24 months

  7. Two years overall survival

    To measure the duration of response to acalabrutinib in combination with R-CHOP over a follow-up period of 2 years

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2018
  2. Study start2 Jun 2017
  3. Primary completion2 Jan 2020
  4. Study completion31 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03571308
Sponsor's protocol ID
RHM CAN 1129
Acronym
ACCEPT
Status last verified
Sep 2023
First submitted
6 Oct 2017
Last updated
28 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing R-CHOP + acalabrutinib in people with Non Hodgkin Lymphoma, run by University Hospital Southampton NHS Foundation Trust at 7 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Dose limiting toxicity of acalabrutinib combined to R-CHOP (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03571308.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.

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