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

  • STATUS
    Recruiting
  • End date
    Mar 31, 2023
  • participants needed
    25
  • sponsor
    Polish Lymphoma Research Group
Updated on 28 January 2021

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.

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.

Details
Condition Lymphoma, Mantle cell lymphoma, Chronic Lymphocytic Leukemia, Lymphocytic Leukemia, Chronic, Non-Hodgkin's Lymphoma, Chronic Graft Versus Host Disease, Adverse Event, Response Rate, chronic graft-versus-host disease, leukemia chronic lymphocytic, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma
Treatment Acalabrutinib 2x100 MG Oral Capsule + alloSCT
Clinical Study IdentifierNCT04716075
SponsorPolish Lymphoma Research Group
Last Modified on28 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Men and women 18 years of age
Relapsing / refractory BTK-inhibitors nave 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 nave 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/l, Platelets < 20 000/l, and hemoglobin < 8 g/dl
\. Breastfeeding or pregnant
\. Concurrent participation in another therapeutic clinical trial
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