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

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ClinicalTrials.gov Identifier: NCT03840512
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Kalytera Therapeutics Israel, Ltd.

Study Description
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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)

Condition or disease Intervention/treatment Phase
Prevention aGVHD Drug: CBD Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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)
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : October 15, 2019
Estimated Study Completion Date : November 15, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Adverse Events (AEs) and serious adverse events (SAEs) Reporting [ Time Frame: Up to day 180 ]
    All AEs will be recorded, whether considered minor or serious, drug-related or not

  2. Cumulative incidence of aGVHD at day 100 post-transplant [ Time Frame: First 100 days after transplant ]
    Cumulative Incidence of Grade B-D aGvHD

  3. Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax [ Time Frame: 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 (PK) profile - Cmax - Maximum Plasma Concentration

  4. Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax [ Time Frame: 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 (PK) profile - Tmax - time to reach maximum plasma concentration

  5. Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag [ Time Frame: 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 (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)

  6. Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t [ Time Frame: 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 (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

  7. Pharmacokinetic parameters of Cannabidiol (CBD) - λz [ Time Frame: 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 (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve

  8. Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2 [ Time Frame: 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 (PK) profile: T1/2 - Terminal elimination half-life

  9. Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞ [ Time Frame: 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 (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity

  10. Cumulative incidence of aGVHD at day 180 post-transplant [ Time Frame: Day 180 post-transplant ]
    Cumulative Incidence of Grade 2-4 aGvHD


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840512


Contacts
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Contact: Sari Sagiv, Ph.D. +97252854444 sari.sagiv@kalytera.co

Locations
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Australia
St Vincent's Hospital Sydney - The Kinghorn Cancer Centre Not yet recruiting
Sydney, Australia, 2010
Contact: Nada Hamad, M.D.    +61293555656    Nada.Hamad@svha.org.au   
Israel
Rambam Health Care - Bone Marrow Transplantation Unit Recruiting
Haifa, Israel, 3109601
Contact: Hila Wildbaum    +972-4-7773248    H_WILDBAUM@rambam.health.gov.il   
Principal Investigator: Tsila Zuckerman, M.D.         
Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center Recruiting
Jerusalem, Israel, 91120
Contact: Liliane Dray    +972-2-677-7803    LILANE@hadassah.org.il   
Principal Investigator: Polina Stepensky, M.D.         
Davidof Cancer Center, Beilinson hospital, Rabin medical center Recruiting
Petach Tikva, Israel, 49100
Contact: Zvi Shivek Shivek    +972-3-9377909    zvish_@clalit.org.il   
Principal Investigator: Liat Shargian, M.D.         
Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit Recruiting
Tel Aviv, Israel
Contact: Sivan Levy    +972-3-6947249    sivanle@tlvmc.gov.il   
Principal Investigator: Ram Ron, M.D.         
Sponsors and Collaborators
Kalytera Therapeutics Israel, Ltd.
More Information
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Responsible Party: Kalytera Therapeutics Israel, Ltd.
ClinicalTrials.gov Identifier: NCT03840512    
Other Study ID Numbers: KAL05
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No