An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)

NCT03840512 | Unknown Phase 2 DMC

• 1 other identifier: KAL05
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 5

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)

Conditions

Prevention aGVHD

Outcome Measures

Primary Outcomes (10)

• 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

• Cumulative incidence of aGVHD at day 100 post-transplant

  Cumulative Incidence of Grade B-D aGvHD

  First 100 days after transplant

• 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

• 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

• 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

• 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

• Pharmacokinetic parameters of Cannabidiol (CBD) - λz

  Pharmacokinetic (PK) profile: λz - 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

• 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

• Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞

  Pharmacokinetic (PK) profile: AUC0-∞ - 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

• Cumulative incidence of aGVHD at day 180 post-transplant

  Cumulative Incidence of Grade 2-4 aGvHD

  Day 180 post-transplant

Study Arms (3)

Oral CBD 75 BID

EXPERIMENTAL

Drug: CBD

Oral CBD 150 BID

EXPERIMENTAL

Drug: CBD

Oral CBD 300 BID

EXPERIMENTAL

Drug: CBD

Interventions

CBD DRUG

CBD + Standard aGVHD prophylaxis calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate (MTX). Subjects transplanted from unrelated donors or from mismatched siblings will also receive anti-T cell globulin.

Oral CBD 150 BID; Oral CBD 300 BID; Oral CBD 75 BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS)
• Age ≥ 18 years
• Karnofsky Score (KS) ≥ 60%
• HSCT-Comorbidity Index (HSCT-CI) score ≤ 3
• No major organ dysfunction
• Myeloablative or reduced intensity conditioning regimen
• Matched (7/8 or 8/8) unrelated donor
• Peripheral blood stem cell graft
• 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.
• Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study.
• Subject's written informed consent

You may not qualify if:

• Malignant hematological disease other than MDS, not in CR
• Myelofibrosis
• Allogeneic transplantation from a matched or mismatched sibling donor
• Cord blood transplantation
• Positive serology for HIV
• Serious psychiatric or psychological disorders
• Any uncontrolled infection at time of registration
• Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines, Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy)
• Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the duration of study participation
• Uncontrolled hepatitis B or active hepatitis C infection.
• QTc\>450ms per Fridericia's correction and Impaired cardiac function or clinically significant cardiac diseases
• Inadequate renal function defined as measured creatinine clearance \> 2.0 mg/dl
• Liver enzymes: ALT and AST \> 3x upper limit of normal
• Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose)
• 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

Sponsors & Collaborators

• Kalytera Therapeutics Israel, Ltd.: lead

Study Sites (5)

St Vincent's Hospital Sydney - The Kinghorn Cancer Centre

Sydney, 2010, Australia

Location

Rambam Health Care - Bone Marrow Transplantation Unit

Haifa, 3109601, Israel

Location

Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center

Jerusalem, 91120, Israel

Location

Davidof Cancer Center, Beilinson hospital, Rabin medical center

Petah Tikva, 49100, Israel

Location

Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit

Tel Aviv, Israel

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2019
• First Posted: February 15, 2019
• Study Start: June 12, 2018
• Primary Completion: November 15, 2022
• Study Completion: December 15, 2022
• Last Updated: September 1, 2021

Record last verified: 2021-08

Locations

IL (4); AU (1)