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

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)

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Prevention aGVHD
• Intervention / Treatment: Drug: CBD

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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, 2010
    • St Vincent's Hospital Sydney - The Kinghorn Cancer Centre
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care - Bone Marrow Transplantation Unit
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center
  • Petach Tikva, Israel, 49100
    • Davidof Cancer Center, Beilinson hospital, Rabin medical center
  • Tel Aviv, Israel
    • Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral CBD 75 BID	Drug: CBD; 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.
Experimental: Oral CBD 150 BID	Drug: CBD; 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.
Experimental: Oral CBD 300 BID	Drug: CBD; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Kalytera Therapeutics Israel, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2018
• Primary Completion (Anticipated): November 15, 2022
• Study Completion (Anticipated): December 15, 2022

Study Registration Dates

• First Submitted: February 10, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: KAL05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No