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

Primary Purpose

Chronic Lymphocytic Leukemia, Chronic Graft-versus-host-disease, Mantle Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
Acalabrutinib 2x100 MG Oral Capsule + alloSCT
Sponsored by
Polish Lymphoma Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring acalabrutinib, Chronic Lymphocytic Leukaemia, allogeneic haematopetic cell transplantation, Chronic Graft-versus-host-disease, Minimal Residual Disease, reduced intensity conditioning, Mantle Cell Disease

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Men and women ≥ 18 years of age.
  2. Relapsing / refractory BTK-inhibitors naïve CLL patients meeting IWCCL criteria for requiring treatment:

    1. after 1-4 therapy lines if del 17 or p53 mutation in >10% of analyzed CLL cells (PB or BM) or
    2. 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
  3. Relapsing / refractory BTK-inhibitors naïve MCL patients with measurable disease or bone marrow involvement revealed in trephine biopsy or
  4. Patients fulfilling criteria 2 or 3, when ibrutinib therapy was initiated, responding to therapy
  5. 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.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  7. 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.
  8. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  9. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

Exclusion Criteria:

  1. Patients failing 5 or more previous therapy lines
  2. 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
  3. 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.
  4. 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.
  5. Impaired hepatic function (as indicated by any of the following):

    1. Serum total bilirubin > 2.5 x upper limit of normal (ULN)
    2. Alanine amino transferase and/or aspartate amino transferase > 2.5 x ULN
    3. Alkaline phosphatase > 2.5 x ULN
  6. Impaired renal function: serum creatinine > 2.5 x ULN
  7. Other concurrent serious diseases that increase Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) > 4
  8. Central nervous system involvement with CLL
  9. Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components).
  10. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
  11. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
  12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
  13. 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
  14. Requiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
  15. 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.
  16. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
  17. History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
  18. 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.
  19. Known history of infection with HIV or any active uncontrolled systemic infection
  20. 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.

  21. ANC < 500/μl, Platelets < 20 000/μl, and hemoglobin < 8 g/dl
  22. Breastfeeding or pregnant.
  23. Concurrent participation in another therapeutic clinical trial.

Sites / Locations

  • Instytut Hematologii i Transfuzjologii
  • Narodowy Intytut Onkologii im. M. Skłodowskiej-Curie Oddział w Krakowie, Pododdział Leczenia Nowotworów Układu Chłonnego
  • Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w GliwicachRecruiting
  • Szpital Kliniczny Przemienienia Pańskiego, Oddział Hematologii i Transplantacji SzpikuRecruiting
  • Narodowy Instytut Onkologii - im. Marii Skłodowskiej- Curie -Państwowy Instytut Badawczy Klinika Nowotworów Układu Chłonnego
  • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytetu MedycznegoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acalabrutinib 2x100mg oral capsule +alloSCT

Arm Description

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

Outcomes

Primary Outcome Measures

Response Rate
Nr of patients with partial and complete response (PR and CR),
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)
Adverse event/serious adverse event incidence
Incidence of adverse events per system

Secondary Outcome Measures

Non-relapse mortality
Nr of patients who died being in continuous remission
Relapse incidence
Nr of patients with return of a disease or the signs and symptoms of a disease after a period of improvement
Progression free survival
Nr of days from assignment in a clinical trial to disease progression or death from any cause

Full Information

First Posted
December 17, 2020
Last Updated
March 31, 2023
Sponsor
Polish Lymphoma Research Group
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT04716075
Brief Title
Acalabrutinib in CLL and MCL Patients Subjected to Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)
Acronym
ACALLO
Official Title
Acalabrutinib in CLL and MCL Patients Subjected to Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 19, 2019 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Polish Lymphoma Research Group
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Multicentre, national
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Acalabrutinib 2x100mg oral capsule +alloSCT
Arm Type
Experimental
Arm Description
Acalabrutinib administered 2x100mg p.o. daily for 3-6 months before alloSCT +acalabrutinib administered 2x100mg p.o. daily for 9 months after alloSCT
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib 2x100 MG Oral Capsule + alloSCT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response Rate
Description
Nr of patients with partial and complete response (PR and CR),
Time Frame
through study completion on average 27 months
Title
Response to therapy Minimum residual disease CR (MRD CR) rate
Description
Nr of patients with minimum residual disease CR (MRD CR) assessed by flow cytometry in peripheral blood (PB) and bone marrow (BM)
Time Frame
through study completion on average 27 months
Title
Adverse event/serious adverse event incidence
Description
Incidence of adverse events per system
Time Frame
acalabrutinib completion or discontinuation plus 30 days of the last acalabrutinib dose
Secondary Outcome Measure Information:
Title
Non-relapse mortality
Description
Nr of patients who died being in continuous remission
Time Frame
through study completion on average 27 months
Title
Relapse incidence
Description
Nr of patients with return of a disease or the signs and symptoms of a disease after a period of improvement
Time Frame
through study completion on average 27 months
Title
Progression free survival
Description
Nr of days from assignment in a clinical trial to disease progression or death from any cause
Time Frame
through study completion on average 27 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wojciech Jurczak, Prof.
Phone
+48126348268
Email
wojciech.jurczak@lymphoma.edu.pl
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Czyż, Prof.
Phone
+ 48 71 7842576
Email
aczyz@onet.eu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sebastian Giebel, Prof.
Organizational Affiliation
Polish Lymphoma Research Organization
Official's Role
Study Chair
Facility Information:
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-776
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Narodowy Intytut Onkologii im. M. Skłodowskiej-Curie Oddział w Krakowie, Pododdział Leczenia Nowotworów Układu Chłonnego
City
Kraków
State/Province
Małopolska
ZIP/Postal Code
31-115
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wojciech Jurczak, MD PhD Prof.
Phone
+48 602 338290
Email
Wojciech Jurczak <wojciech.jurczak@lymphoma.edu.pl>
Facility Name
Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach
City
Gliwice
State/Province
Slaskie
ZIP/Postal Code
44-101
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacek Najda, MD PhD
Phone
+48 501315101
Email
jacek.najda@io.gliwice.pl
First Name & Middle Initial & Last Name & Degree
Malgorzata Sobczyk-Kruszelnicka, MD
Phone
+48600048575
Email
Małgorzata Sobczyk-Kruszelnicka <Malgorzata.Kruszelnicka@io.gliwice.pl>
First Name & Middle Initial & Last Name & Degree
Sebastian Giebel Giebel, Prof.
First Name & Middle Initial & Last Name & Degree
Jacek Najda, MD PhD
First Name & Middle Initial & Last Name & Degree
Malgorzata Sobczyk-Kruszelnicka, MD
Facility Name
Szpital Kliniczny Przemienienia Pańskiego, Oddział Hematologii i Transplantacji Szpiku
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
60-569
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lidia Gil, MD PhD Prof.
Phone
+48 601 583 587
Email
lidia.gil@skpp.edu.pl
Facility Name
Narodowy Instytut Onkologii - im. Marii Skłodowskiej- Curie -Państwowy Instytut Badawczy Klinika Nowotworów Układu Chłonnego
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanna Romejko-Jarosińska, MD PhD
Phone
+48 22-546-2448
Email
Joanna.Romejko-Jarosinska@pib-nio.pl
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytetu Medycznego
City
Wrocław
ZIP/Postal Code
50-369
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Czyż, MD, PhD, Prof
Phone
+48 601 753 371
Email
a.czyz <a.czyz@umed.wroc.pl>
First Name & Middle Initial & Last Name & Degree
Agnieszka Szeremet, MD PhD
Email
Agnieszka Szeremet <agnieszka.szeremet@wp.pl>

12. IPD Sharing Statement

Plan to Share IPD
No

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

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