Acalabrutinib for GVHD Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia

NCT04961801 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: PSCI-18-128
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

GVHD remains a major cause of morbidity and mortality following SCT. The current standard of care for prophylaxis against GVHD includes tacrolimus and methotrexate. This study proposes to utilize acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, for GVHD prophylaxis following allogeneic SCT. The hypothesis is that the addition of acalabrutinib to our institutional standard GVHD prophylaxis (tacrolimus and methotrexate) is safe, feasible, and effective in reducing both the incidence and severity of acute GVHD.

Conditions

Lymphoma; Leukemia

Keywords

Graft-Versus-Host Disease Prophylaxis

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity

  Dose-limiting toxicity of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study

  30 days

• Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) of acalabrutinib in combination with tacrolimus and methotrexate in early SCT for Phase I part of the study

  30 days

• acute GVHD grade II-IV

  Incidence of acute GVHD grade II-IV by day 180 for Phase II part of the study

  180 days

Study Arms (1)

Acalabrutinib in combination with tacrolimus and methotrexate

EXPERIMENTAL

1. Phase I: To determine the maximum tolerated dose (MTD) of Acalabrutinib in combination with tacrolimus and methotrexate for Phase II. 2. Phase II: To determine if acalabrutinib in combination with tacrolimus and methotrexate is safe and effective in reducing acute GVHD rate.

Drug: Acalabrutinib, tacrolimus, methotrexate

Interventions

Acalabrutinib, tacrolimus, methotrexate DRUG

For Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation in Lymphomas and Leukemia

Acalabrutinib in combination with tacrolimus and methotrexate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness and ability to sign the study-specific informed consent form
• Willingness to comply with all study procedures and attend all study visits.
• Participant with (a) B-cell malignancies or (b) AML (CD117 positive) who are undergoing allogeneic SCT at Penn State Cancer Institute from an 8/8 matched unrelated donor. Donor selection and screening criteria are to comply with 21 CRF Part 1271.
• Male or female participant, age ≥ 18 and ≤ 75 years.
• Ability to swallow oral medication.
• Women of childbearing potential (WOCP) as defined as not surgically sterile or not postmenopausal must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 7 days of beginning the condition regimen.
• Men and WOCP must agree to use 2 medically accepted method of contraception and must agree to continue use this method while on the trial and through at least one week after the last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) withdrawal, spermicides only, or lactational amenorrhea are not acceptable methods of contraception. WOCP must use a medically accepted method of contraception and must agree to continue use this method from the time of signing the informed consent through at least one week after the last dose of study drug.
• Karnofsky Performance Scale (KPS) equal to or greater than 70%.

You may not qualify if:

• Renal dysfunction with eGFR \<30/mL/minute/1.73 m2 by Cockroft-Gault formula.
• Participant requires warfarin or vitamin K antagonist within one week of acalabrutinib administration.
• Participant requires treatment with a strong cytochrome P450 3A inducer or inhibitor.
• Treatment with post-transplant cyclophosphamide
• Treatment with any other investigational products within 21 days of conditioning regimen.
• Known hypersensitivity to acalabrutinib, tacrolimus and methotrexate and their excipients.
• Active uncontrolled infections
• Human immunodeficiency virus (HIV) positivity.
• Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are 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 to be eligible. Those who are hepatitis C PCR positive will be excluded.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
• Diagnosed or treated for another malignancy within 2 years before study registration or previously diagnosed with another malignancy and have any evidence of residual disease. Participant with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Participant with coagulopathy or bleeding disorder.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment (ALT and/or AST more than 3x greater than upper limit of normal, Total Bilirubin more than 2x greater than upper limit of normal)
• Uncontrolled high blood pressure (i.e., systolic blood pressure \> 180 mm Hg, diastolic blood pressure \> 95 mm Hg).
• Uncontrolled or symptomatic cardiac arrhythmia

Sponsors & Collaborators

• Shin Mineishi: lead
• Milton S. Hershey Medical Center: collaborator

MeSH Terms

Conditions

Lymphoma; Leukemia

Interventions

acalabrutinib; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Hematology/Oncology

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: July 14, 2021
• Study Start: March 1, 2022
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 8, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share