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Chronic Lymphocytic LeukemiaPhase 2ACALLONCT04716075

Acalabrutinib in CLL and MCL Patients Subjected to Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)

A Phase 2 study testing Acalabrutinib 2x100 MG Oral Capsule + alloSCT in people with Chronic Lymphocytic Leukemia and Chronic Graft-versus-host-disease, run by Polish Lymphoma Research Group at 6 sites in Poland.

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

In this phase II multicenter trial we plan to use acalabrutinib before and after allogeneic hematopoietic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) in patients with refractory/relapsed MCL and CLL with poor prognostic factors. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Acalabrutinib 2x100 MG Oral Capsule + alloSCT
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
6 sitesPoland
Study dates
19 Aug 2019to 30 Jul 2024
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women ≥ 18 years of age.
  • Relapsing / refractory BTK-inhibitors naïve CLL patients meeting IWCCL criteria for requiring treatment:
  • after 1-4 therapy lines if del 17 or p53 mutation in >10% of analyzed CLL cells (PB or BM) or
  • after 2-4 therapy lines if high risk CLL (refractory or less than 24 months response to the last immunochemotherapy) or Confidential Page 15 of 82 Study Protocol v. 1.5 dated 06.07.2018
  • Relapsing / refractory BTK-inhibitors naïve MCL patients with measurable disease or bone marrow involvement revealed in trephine biopsy or
  • Patients fulfilling criteria 2 or 3, when ibrutinib therapy was initiated, responding to therapy
Show all 11Show fewer
  • Patient qualified for allo SCT procedure by the transplant center participating in the trial with identified sibling donor or initiated Poltransplant search for matched unrelated donor.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib and for 6 months after the transplant procedure if performed. Males who are sexually active must use highly effective methods of contraception during treatment and for 6 months after the transplant procedure if performed.
  • 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

  • Patients failing 5 or more previous therapy lines
  • 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
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or Confidential Page 16 of 82 Study Protocol v. 1.5 dated 06.07.2018 any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification (NYHA). 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.
  • Impaired hepatic function (as indicated by any of the following):
  • Serum total bilirubin > 2.5 x upper limit of normal (ULN)
Show all 27Show fewer
  • Alanine amino transferase and/or aspartate amino transferase > 2.5 x ULN
  • Alkaline phosphatase > 2.5 x ULN
  • Impaired renal function: serum creatinine > 2.5 x ULN
  • Other concurrent serious diseases that increase Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) > 4
  • Central nervous system involvement with CLL
  • 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).
  • Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
  • Requiring or receiving a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer (see appendix 3 for a complete list) Confidential Page 17 of 82 Study Protocol v. 1.5 dated 06.07.2018
  • Requiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
  • Requiring proton pump inhibitors (e.g., 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.
  • Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
  • 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 30 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.
  • Known history of infection with HIV or any active uncontrolled systemic infection
  • 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.
  • 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.
  • ANC < 500/μl, Platelets < 20 000/μl, and hemoglobin < 8 g/dl
  • Breastfeeding or pregnant.
  • Concurrent participation in another therapeutic clinical trial.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Poland6 sites
  • Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach

    Gliwice, Silesian Voivodeship, 44-101

  • Narodowy Intytut Onkologii im. M. Skłodowskiej-Curie Oddział w Krakowie, Pododdział Leczenia Nowotworów Układu Chłonnego

    Krakow, Małopolska, 31-115

  • Szpital Kliniczny Przemienienia Pańskiego, Oddział Hematologii i Transplantacji Szpiku

    Poznan, Greater Poland Voivodeship, 60-569

  • Instytut Hematologii i Transfuzjologii

    Warsaw, Masovian Voivodeship, 02-776

  • Narodowy Instytut Onkologii - im. Marii Skłodowskiej- Curie -Państwowy Instytut Badawczy Klinika Nowotworów Układu Chłonnego

    Warsaw, 02-781

  • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytetu Medycznego

    Wroclaw, 50-369

Other trials in Poland

About this study

In this phase II multicenter trial we plan to use acalabrutinib before and after allogeneic hematopoietic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) in patients with refractory/relapsed MCL and CLL with poor prognostic factors. Acalabrutinib will be used before alloSCT with the intention to reduce tumor burden and after transplant to augment disease control.

Read the detailed description

In this phase II multicenter trial we plan to use acalabrutinib before and after allogeneic hematopoietic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) in patients with refractory/relapsed MCL and CLL with poor prognostic factors. Acalabrutinib will be used before alloSCT with the intention to reduce tumor burden and after transplant to augment disease control. Since chronic GvHD is mediated by activated B lymphocytes, we also speculate that the drug as a BTK inhibitor may reduce the severity and incidence of chronic graft-versus-host disease (GvHD) after alloSCT, as it was shown for ibrutinib.

Best response to therapy and safety issues will be the primary target of this small trial (25 transplanted pts).TEAE and SAE of acalabrutinib in patients after alloSCT that was not previously assessed.

We hypothesize that this treatment will improve the efficacy of the alloSCT - this issue will be addressed by serial minimal residual disease (MRD) evaluation in peripheral blood and bone marrow. This treatment strategy could significantly improve the outcome of poor prognosis MCL and CLL patients.

Being tested
Acalabrutinib 2x100 MG Oral Capsule + alloSCT
Keywords
acalabrutinib, Chronic Lymphocytic Leukaemia, allogeneic haematopetic cell transplantation, Chronic Graft-versus-host-disease, Minimal Residual Disease, reduced intensity conditioning, Mantle Cell Disease
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Bronchiolitis Obliterans Syndrome, Lymphoma, Mantle-Cell, Leukemia, B-Cell, Neoplasm, Residual

What participants receive

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

  • Acalabrutinib 2x100 MG Oral Capsule + alloSCTDrug

    Acalabrutinib 100 mg caps will be administered twice daily for 3-6 months before the intended alloSCT. After restarting acalabrutinib (2x100 mg daily) after the transplant procedure it will be administered for further 9 months. In patients who do not have an acceptable donor acalabrutinib will be administered until disease progression or unacceptable toxicity.

Study groups in NCT04716075
Study groupRoleWhat they receive
Acalabrutinib 2x100mg oral capsule +alloSCTExperimentalAcalabrutinib administered 2x100mg p.o. daily for 3-6 months before alloSCT +acalabrutinib administered 2x100mg p.o. daily for 9 months after alloSCT
Receives: Drug: Acalabrutinib 2x100 MG Oral Capsule + alloSCT

What is being measured

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

  1. Response Rate

    Nr of patients with partial and complete response (PR and CR),

    Measured: through study completion on average 27 months

  2. Response to therapy Minimum residual disease CR (MRD CR) rate

    Nr of patients with minimum residual disease CR (MRD CR) assessed by flow cytometry in peripheral blood (PB) and bone marrow (BM)

    Measured: through study completion on average 27 months

  3. Adverse event/serious adverse event incidence

    Incidence of adverse events per system

    Measured: acalabrutinib completion or discontinuation plus 30 days of the last acalabrutinib dose

Secondary outcomes (3)
  1. Non-relapse mortality

    Nr of patients who died being in continuous remission

    Measured: through study completion on average 27 months

  2. Relapse incidence

    Nr of patients with return of a disease or the signs and symptoms of a disease after a period of improvement

    Measured: through study completion on average 27 months

  3. Progression free survival

    Nr of days from assignment in a clinical trial to disease progression or death from any cause

    Measured: through study completion on average 27 months

Timeline

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

  1. First posted20 Jan 2021
  2. Study start19 Aug 2019
  3. Primary completion30 Jun 2024
  4. Study completion30 Jul 2024

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
Model description
Multicentre, national
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04716075
Sponsor's protocol ID
PLRG12
Acronym
ACALLO
Status last verified
Jan 2025
First submitted
17 Dec 2020
Last updated
16 Jan 2025
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 2 study testing Acalabrutinib 2x100 MG Oral Capsule + alloSCT in people with Chronic Lymphocytic Leukemia and Chronic Graft-versus-host-disease, run by Polish Lymphoma Research Group at 6 sites in Poland.

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 11 inclusion and 27 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 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Poland. 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?

Response Rate (time frame: through study completion on average 27 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?
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 16 Jan 2025.

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