Study register · detailPhase-II-Studie (unkontrolliert mit historischen Kontrollen) · Cancer · 2015
Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.
Yeshurun et al.·Biology of Blood and Marrow Transplantation
Clear benefitGRADEModerate81 citations
Samplen = 48 Pat.
DurationMedian 16 months
Control101 historical control patients under…
EndpointAcute GVHD grade II–IV
Blindingoffen
DesignPhase-II-Studie (unkontrolliert mit historischen Kontrollen)
Cannabinoidcbd
Max. dose300.0 mg
Routeoral
”Key finding
CBD in addition to standard prophylaxis significantly reduced the incidence of acute GVHD compared with historical controls (HR 0,3; p=0,0002).
Summary
n=48 alloHCT patients (79 % acute leukemia/MDS), CBD 300 mg/day orally (day −7 to +30) in addition to standard GVHD prophylaxis; cumulative incidence of acute GVHD grade II–IV by day 100: 12,1 %, grade III–IV: 5 %; no patient developed acute GVHD while taking CBD. Hazard ratio for grade II–IV GVHD vs. 101 historical controls: HR=0,3 (p=0,0002). Non-relapse mortality at day 100: 8,6 %; no CBD-associated grade 3–4 adverse events.
InterventionCannabidiol (CBD) 300 mg/day orally, starting 7 days before transplantation until day 30, in addition to standard GVHD prophylaxis (cyclosporine + short methotrexate regimen)
C
Control101 historical control patients under standard GVHD prophylaxis
O
OutcomeCumulative incidence of acute GVHD grade II–IV by day 100: 12,1%; hazard ratio for grade II–IV acute GVHD vs. historical controls: 0,3 (p=0,0002)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeClear benefit
Citations / year★★★★★
Authors
Yeshurun M, Shpilberg O, Herscovici C, Shargian L, Dreyer J, Peck A, Israeli M, Levy-Assaraf M, Gruenewald T, Mechoulam R, Raanani P, Ram R.
Design: Phase-II-Studie (unkontrolliert mit historischen Kontrollen)
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Abstract
Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted. (clinicaltrials.gov: NCT01385124).