Prevention aGVHD Clinical Trial
Official title:
A Phase 2a, Open-label, Multicenter, Study to Evaluate the Pharmacokinetic (PK), Safety and Efficacy of Multiple Doses of Cannabidiol for the Prevention of aGVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
| Verified date | August 2021 |
| Source | Kalytera Therapeutics Israel, Ltd. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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)
| Status | Active, not recruiting |
| Enrollment | 36 |
| Est. completion date | December 15, 2022 |
| Est. primary completion date | November 15, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 ß-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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | St Vincent's Hospital Sydney - The Kinghorn Cancer Centre | Sydney | |
| Israel | 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 | Petach Tikva | |
| Israel | Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit | Tel Aviv |
| Lead Sponsor | Collaborator |
|---|---|
| Kalytera Therapeutics Israel, Ltd. |
Australia, Israel,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Adverse Events (AEs) and serious adverse events (SAEs) Reporting | All AEs will be recorded, whether considered minor or serious, drug-related or not | Up to day 180 | |
| Primary | Cumulative incidence of aGVHD at day 100 post-transplant | Cumulative Incidence of Grade B-D aGvHD | First 100 days after transplant | |
| Primary | Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax | Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration | 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 | |
| Primary | Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax | Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration | 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 | |
| Primary | 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) | 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 | |
| Primary | 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 | 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 | |
| Primary | Pharmacokinetic parameters of Cannabidiol (CBD) - ?z | Pharmacokinetic (PK) profile: ?z - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve | 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 | |
| Primary | Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2 | Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life | 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 | |
| Primary | Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-8 | Pharmacokinetic (PK) profile: AUC0-8 - area under the plasma concentration-time curve extrapolated to infinity | 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 | |
| Primary | Cumulative incidence of aGVHD at day 180 post-transplant | Cumulative Incidence of Grade 2-4 aGvHD | Day 180 post-transplant |