Extended Use of Cannabidiol for the Prevention of Graft-versus-host-disease

Study Overview
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Brief Summary
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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.

Official Title
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Extended Use of Cannabidiol for the Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation

Conditions
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Graft vs Host Disease

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: cyclosporine
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute leukemia in complete remission Myeloablative conditioning Matched or one antigen or allele mismatched sibling or unrelated donor Exclusion Criteria: History of psychosis Bronchial asthma

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol arm<br>Patients undergoing an allogeneic hematopoietic cell transplantation will be given standard GVHD prophylaxis comprising cyclosporine and a short course of methotrexate plus CBD 150 mg BID starting 7 days before transplantation until day 100. | Drug: Cannabidiol<br>* 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.<br>* Other names: CBD;Drug: cyclosporine<br> <br> Drug: Methotrexate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non relapse mortality |  | 12 months | 
| Relapse rate |  | 12 months | 
| Overall survival |  | 12 months | 
| Adherence to study protocol | Percentage of doses actually taken as reported by patients | Until day 100 | 
| Disease free and immunosuppression free survival by 12 months |  | 12 months |