AzTrials
AzTrials

Non-hodgkin Lymphoma,B CellPhase 2NCT04094142

Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

A Phase 2 study testing Acalabrutinib in people with Non-hodgkin Lymphoma,B Cell, run by Seoul National University Hospital at 1 site in South Korea.

Completed

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

Official record
Search all trials

Trial summary

NCCN guidelines for B cell lymphoma suggest that patients with relapsed/refractory aggressive NHL who are candidate for high-dose therapy should receive combination of cytotoxic chemotherapies as 2nd line treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-hodgkin Lymphoma,B Cell
What is being tested?
Acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteSouth Korea
Study dates
9 Jul 2019to 15 May 2022
Phase
Phase 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women ≥ 18 years of age.
  • Diagnosed with aggressive B cell non-Hodgkin lymphoma
  • Diffuse large B cell lymphoma (Both GCB and non-GCB)
  • : GCB type should not be more than 40% (N=26) of whole study population (Would limit number of GCB patients by maximum of 26)
  • Primary mediastinal B cell lymphoma
  • Transformed follicular lymphoma
Show all 15Show fewer
  • Small lymphocytic lymphoma with Richter transformation
  • Failed previous treatments and last dose administered must be more than 2-week ahead from enrollment
  • Should have received anti-CD20 based chemotherapy previously
  • Failed at least two lines of therapy if patient is candidate for autologous stem cell transplantation
  • Failed frontline therapy if patient is ineligible for autologous stem cell transplantation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Woman of childbearing potential (WOCBP) who are sexually active must have 2 negative urine hCG test prior to first dose, then every week for the first month of study period, then every 4 weeks afterwards during treatment period if menses are regular or every 2 weeks if menses are irregular. Urine hCG test must be done 4 weeks after the last dose of acalabrutinib, lenalidomide and rituximab. WOCBP must use 2 methods including at least 1 highly effective method of contraception for 4 weeks prior to first dose, during treatment period and for 4 weeks after the last dose of acalabrutinib, lenalidomide and for 12 months after the last dose of rituximab. Men who are sexually active must use condoms during treatment period and 4 weeks after the last dose of any study drug.
  • 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 and authorization to use protected health information.

Who cannot join

  • Diagnosed with mantle cell lymphoma
  • Previously treated with more than four lines of chemotherapy (Consolidative autologous stem cell transplantation is deemed as the same line therapy)
  • Previously treated with allogeneic hematopoietic stem cell transplantation within 6 months
  • GVHD requiring treatment
  • Patient who cannot take drug per oral
  • Known resistance to both BTK inhibitor and lenalidomide (Progression free survival to both BTK inhibitor and lenalidomide < 6 months)
Show all 29Show fewer
  • Known resistant mutation to BTK inhibitor (BTKC481S and PLGCR665W)
  • Prior malignancy (or any other malignancy that requires active treatment), 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 ≥ 5 years or which will not limit survival to < 5 years.
  • Clinically 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. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  • Known history of infection with HIV or any uncontrolled active systemic infection (eg, bacterial, viral or fungal).
  • Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components).
  • Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
  • Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
  • Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
  • Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
  • History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
  • Major surgical procedure within 28 days of first dose of study drug. Note: 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.
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Those who are positive only for anti-HBc and negative for HbsAg and hepatitis B PCR need to receive adequate antiviral prophylaxis for hepatitis B during the study period.
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.
  • Active tuberculosis (history of exposure or history of positive tuberculin test; plus presence of clinical symptoms, physical or radiographic findings). Subjects with latent tuberculosis infection who are deemed to require treatment by the investigator are not eligible.
  • Uncontrolled active infection as determined by the investigator.
  • WBC < 3,000 /μL, ANC < 1,000 /μL, Platelets < 75,000 /μL, or Hemoglobin < 9.0 g/dL. Correction with transfusion within 2 weeks is not allowed.
  • Total bilirubin > 2 x ULN, or AST, ALT > 3 x ULN
  • Cr > 1.5 x ULN or CLcr < 30 mL/min/1.73m2
  • Breastfeeding or pregnant.
  • Concurrent participation in another therapeutic clinical trial.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Seoul National University Hospital

    Seoul, 03080

Other trials in South Korea

About this study

Official title: Phase II Trial of Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

NCCN guidelines for B cell lymphoma suggest that patients with relapsed/refractory aggressive NHL who are candidate for high-dose therapy should receive combination of cytotoxic chemotherapies as 2nd line treatment. However, proportion of patients who are adequately salvaged by second line chemotherapy and high-dose chemotherapy with stem cell rescue is unsatisfactory. Moreover, many fragile patients are unfit for salvage cytotoxic chemotherapy and/or high-dose chemotherapy. Hence, most of patients with relapsed/refractory aggressive B-cell NHL is ultimately candidate for less-cytotoxic drugs with targeted approach. This trial is phase II trial of acalabrutinib in combination with rituximab and lenalidomide for these patients.

Being tested
Acalabrutinib

What participants receive

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

  • AcalabrutinibDrug

    Also called Lenalidomide, Rituximab

    Acalabrutinib, lenalidomide, rituximab will be given as described in the "Arms" decriptions. Day 1 to day 28 is considered one cycle, and cycles will be repeated every 4-weeks, for 6 cycles.

    After 6 cycles, maintenance of acalabrutinib 100mg bid will be administered up to 1 year for subjects whose best responses- to the regimen are partial response or complete remission.

Study groups in NCT04094142
Study groupRoleWhat they receive
Treatment armExperimentalAcalabrutinib is provided as hard gelatin capsules for oral administration. Acalabrutinib 100 mg will be administered approximately every 12 hours from day 1 to day 28 Rituximab is provided as single-use vials for intravenous administration only. Rituximab 375 mg/m2 will be administered on day 1. Lenalidomide is provided as opaque hard capsules for oral administration. Lenalidomide 20 mg will be administered once daily from day 1 to day 21
Receives: Drug: Acalabrutinib

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Lugano criteria

    Measured: within 4 weeks after the 6 cycles of combination therapy (each cycle is 28 days)

Secondary outcomes (4)

  1. Duration of response

    Measured: Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)

  2. Complete remission rate

    Measured: Response will be assessed at Week 8, 16, 24 (± 7 days)

  3. Progression free survival

    Measured: Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)

  4. Overall survival

    Measured: Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)

Timeline

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

  1. First posted18 Sep 2019
  2. Study start9 Jul 2019
  3. Primary completion15 May 2022
  4. Study completion15 May 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04094142
Sponsor's protocol ID
1811-092-988
Status last verified
Apr 2023
First submitted
19 Jul 2019
Last updated
18 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Park C, Lee HS, Kang KW, Lee WS, Do YR, Kwak JY, Shin HJ, Kim SY, Yi JH, Lim SN, Lee JO, Yang DH, Jang H, Choi B, Lim J, Sun CH, Byun JM, Yoon SS, Koh Y. Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial. Nat Commun. 2024 Mar 30;15(1):2776. doi: 10.1038/s41467-024-47198-4.

    PubMed 38555311

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib in people with Non-hodgkin Lymphoma,B Cell, run by Seoul National University Hospital at 1 site in South Korea.

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 15 inclusion and 29 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 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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 phase mean?

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?

Objective Response Rate (ORR) (time frame: within 4 weeks after the 6 cycles of combination therapy (each cycle is 28 days)). 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 NCT04094142, which also lists 1 linked publication.

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 18 Apr 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in