Clinical trial NCT03840512: An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prevention aGVHD
Lead sponsor: Kalytera Therapeutics Israel, Ltd.
Sponsor class: INDUSTRY
First posted: 2019-02-15
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events (AEs) and serious adverse events (SAEs) Reporting
timeFrame: Up to day 180
measure: Cumulative incidence of aGVHD at day 100 post-transplant
timeFrame: First 100 days after transplant
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - λz
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2
timeFrame: 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
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞
timeFrame: 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
measure: Cumulative incidence of aGVHD at day 180 post-transplant
timeFrame: Day 180 post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St Vincent's Hospital Sydney - The Kinghorn Cancer Centre
city: Haifa
country: Israel
facility: Rambam Health Care - Bone Marrow Transplantation Unit
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center
city: Petach Tikva
country: Israel
facility: Davidof Cancer Center, Beilinson hospital, Rabin medical center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit
Study officials:
References: