Graft vs Host Disease
Conditions
Brief summary
Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. In a recent prospective phase II study (NCT01385124) 48 consecutive adult patients undergoing allogeneic hematopoietic cell transplantation were given CBD 300 mg/day starting 7 days before transplantation until day 30, on top of standard GVHD prophylaxis consisting of cyclosporine and a short course of methotrexate. There were no grade 3-4 toxicities attributed to CBD. None of the patients developed acute GVHD while consuming CBD. With a median follow-up of 16 months, the cumulative incidence rates of grade 2-4 and grade 3-4 acute GVHD by day 100 were 12.1% and 5%, respectively. Compared to 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grade 2-4 acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was 0.3 (p=0.0002). Among patients surviving more than 100 days, the cumulative incidence of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The aim of this study is to explore the safety and efficacy of extended use of CBD until day 100 in the prevention of acute and chronic GVHD.
Interventions
DRUGCannabidiol
Patients will receive standard GVHD prophylaxis consisting of cyclosporine A twice daily starting on day -1 with target trough levels of 200-400 ng/mL and a short course of methotrexate (15 mg/ m2 on day 1 and 10 mg/ m2 on days days 3 and 6). Patients transplanted from unrelated donors will receive ATG Fresenius at a low dose of 5 mg/kg on days -3 to -1. Patients will be given oral CBD 150 mg BID starting 7 days before transplantation until day 100.
DRUGcyclosporine
DRUGMethotrexate
Sponsors
Rabin Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Acute leukemia in complete remission 2. Myeloablative conditioning 3. Matched or one antigen or allele mismatched sibling or unrelated donor
Exclusion criteria
1. History of psychosis 2. Bronchial asthma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of grade 2-4 and grade 3-4 acute GVHD by day 100 | 100 days |
| grade 3-4 adverse effects attributed to CBD consumption | 180 days |
| Incidence of overall chronic GVHD and moderate to severe chronic GVHD by 12 months | 12 months |
| Incidence of late onset acute GVHD | 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non relapse mortality | 12 months | — |
| Disease free and immunosuppression free survival by 12 months | 12 months | — |
| Relapse rate | 12 months | — |
| Overall survival | 12 months | — |
| Adherence to study protocol | Until day 100 | Percentage of doses actually taken as reported by patients |
Contacts
Primary ContactMoshe Yeshurun, MD
Backup ContactLiat Shargian, MD
Outcome results
None listed