Prevention aGVHD
Conditions
Brief summary
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)
Detailed description
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.
Interventions
DRUGCBD
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.
Sponsors
Kalytera Therapeutics Israel, Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS) 2. Age ≥ 18 years 3. Karnofsky Score (KS) ≥ 60% 4. HSCT-Comorbidity Index (HSCT-CI) score ≤ 3 5. No major organ dysfunction 6. Myeloablative or reduced intensity conditioning regimen 7. Matched (7/8 or 8/8) unrelated donor 8. Peripheral blood stem cell graft 9. Female subjects of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. 10. Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study. 11. Subject's written informed consent
Exclusion criteria
1. Malignant hematological disease other than MDS, not in CR 2. Myelofibrosis 3. Allogeneic transplantation from a matched or mismatched sibling donor 4. Cord blood transplantation 5. Positive serology for HIV 6. Serious psychiatric or psychological disorders 7. Any uncontrolled infection at time of registration 8. Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines, Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy) 9. Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the duration of study participation 10. Uncontrolled hepatitis B or active hepatitis C infection. 11. QTc\>450ms per Fridericia's correction and Impaired cardiac function or clinically significant cardiac diseases 12. Inadequate renal function defined as measured creatinine clearance \> 2.0 mg/dl 13. Liver enzymes: ALT and AST \> 3x upper limit of normal 14. Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose) 15. Treatment with another investigational drug, biological agent, or device within 30 days of first dose, or investigational cell therapy within 6 months of first dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) and serious adverse events (SAEs) Reporting | Up to day 180 | All AEs will be recorded, whether considered minor or serious, drug-related or not |
| Cumulative incidence of aGVHD at day 100 post-transplant | First 100 days after transplant | Cumulative Incidence of Grade B-D aGvHD |
| Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax | 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 (PK) profile - Cmax - Maximum Plasma Concentration |
| Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax | 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 (PK) profile - Tmax - time to reach maximum plasma concentration |
| Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag | 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 (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ) |
| Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t | 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 (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 |
| Pharmacokinetic parameters of Cannabidiol (CBD) - λz | 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 (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve |
| Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2 | 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 (PK) profile: T1/2 - Terminal elimination half-life |
| Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞ | 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 (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity |
| Cumulative incidence of aGVHD at day 180 post-transplant | Day 180 post-transplant | Cumulative Incidence of Grade 2-4 aGvHD |
Countries
Australia, Israel
Outcome results
None listed