A prospective, open-label, phase 2a study, to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of multiple doses of Cannabidiol (CBD) in participants Graft-Versus-Host Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)
The study contains 3 cohorts of 12 participants each: All participants will be orally administered for 105 days with CBD at doses of 75, 150 or 300 mg (PO) BID for the prevention of acute GVHD (aGVHD) following allogeneic HSCT. In addition to the study drug, all participants will receive standard aGVHD prophylaxis consisting of a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate (MTX). After completion of 105 treatment days, the participant will be followed-up until day 180.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
36
CBD + Standard aGVHD prophylaxis calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate (MTX). Subjects transplanted from unrelated donors or from mismatched siblings will also receive anti-T cell globulin.
St Vincent's Hospital Sydney - The Kinghorn Cancer Centre
Sydney, Australia
Rambam Health Care - Bone Marrow Transplantation Unit
Haifa, Israel
Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center
Jerusalem, Israel
Davidof Cancer Center, Beilinson hospital, Rabin medical center
Petah Tikva, Israel
Adverse Events (AEs) and serious adverse events (SAEs) Reporting
All AEs will be recorded, whether considered minor or serious, drug-related or not
Time frame: Up to day 180
Cumulative incidence of aGVHD at day 100 post-transplant
Cumulative Incidence of Grade B-D aGvHD
Time frame: First 100 days after transplant
Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax
Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax
Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag
Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t
Pharmacokinetic (PK) profile - AUC0-t - area under the plasma concentration-time curve (AUC0-t) up to the last quantifiable concentration (LOQ) from time of administration (t=0) up to the selected
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Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit
Tel Aviv, Israel
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - λz
Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2
Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞
Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity
Time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
Cumulative incidence of aGVHD at day 180 post-transplant
Cumulative Incidence of Grade 2-4 aGvHD
Time frame: Day 180 post-transplant