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

NCT04716075 | Completed Phase 2 DMC

• 1 other identifier: PLRG12
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 6

Brief 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. Acalabrutinib will be used before alloSCT with the intention to reduce tumor burden and after transplant to augment disease control.

Conditions

Chronic Lymphocytic Leukemia; Chronic Graft-versus-host-disease; Mantle Cell Lymphoma; Adverse Event; Response Rate

Keywords

acalabrutinib; Chronic Lymphocytic Leukaemia; allogeneic haematopetic cell transplantation; Chronic Graft-versus-host-disease; Minimal Residual Disease; reduced intensity conditioning; Mantle Cell Disease

Outcome Measures

Primary Outcomes (3)

• Response Rate

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

  through study completion on average 27 months

• 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)

  through study completion on average 27 months

• Adverse event/serious adverse event incidence

  Incidence of adverse events per system

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

Secondary Outcomes (3)

• Non-relapse mortality

  through study completion on average 27 months

• Relapse incidence

  through study completion on average 27 months

• Progression free survival

  through study completion on average 27 months

Study Arms (1)

Acalabrutinib 2x100mg oral capsule +alloSCT

EXPERIMENTAL

Acalabrutinib administered 2x100mg p.o. daily for 3-6 months before alloSCT +acalabrutinib administered 2x100mg p.o. daily for 9 months after alloSCT

Drug: Acalabrutinib 2x100 MG Oral Capsule + alloSCT

Interventions

Acalabrutinib 2x100 MG Oral Capsule + alloSCT DRUG

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.

Acalabrutinib 2x100mg oral capsule +alloSCT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Polish Lymphoma Research Group: lead
• AstraZeneca: collaborator

Study Sites (6)

Szpital Kliniczny Przemienienia Pańskiego, Oddział Hematologii i Transplantacji Szpiku

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, 02-776, Poland

Location

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

Krakow, Małopolska, 31-115, Poland

Location

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

Gliwice, Silesian Voivodeship, 44-101, Poland

Location

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

Warsaw, 02-781, Poland

Location

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

Wroclaw, 50-369, Poland

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Bronchiolitis Obliterans Syndrome; Lymphoma, Mantle-Cell; Leukemia, B-Cell; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Lymphoma, Non-Hodgkin; Lymphoma; Neoplastic Processes

Study Officials

• Sebastian Giebel, Prof.

  Polish Lymphoma Research Organization

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Multicentre, national

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: January 20, 2021
• Study Start: August 19, 2019
• Primary Completion: June 30, 2024
• Study Completion: July 30, 2024
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (6)