RECRUITING

Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation

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Conditions

CandidemiaMycosesFungal InfectionFungemiaInvasive CandidiasisPneumocystisMold InfectionInvasive Fungal DiseaseProphylaxis of Invasive Fungal InfectionsAspergillusCandidiasisCandidiasis, InvasiveSepsisBlood and Marrow Transplant (BMT)InfectionInvasive Fungal InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesFluconazolePosaconazoleCaspofunginTrimethoprim-sulfamethoxazole (TMP/SMX)EchinocandinsAntifungal Agents14-alpha Demethylase InhibitorsCytochrome P-450 Enzyme InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionSteroid Synthesis InhibitorsPhysiological Effects of DrugsCytochrome P-450 CYP2C9 InhibitorsCytochrome P-450 CYP2C19 InhibitorsRezafunginAnti-Infective Agents

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the prevention of invasive fungal diseases when compared to the standard antimicrobial regimen.

Official Title

A Phase 3, Multicenter, Randomized, Double-Blind Study of the Efficacy and Safety of Rezafungin for Injection Versus the Standard Antimicrobial Regimen to Prevent Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation (The ReSPECT Study)

Quick Facts

Study Start:2020-05-11
Study Completion:2025-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04368559

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Willing and able to provide written informed consent.
  2. 2. Males or females ≥18 years of age.
  3. 3. Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
  4. 4. Diagnosed with 1 of the following underlying diseases:
  5. 1. Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
  6. 2. Acute lymphoblastic leukemia, in first or second complete remission.
  7. 3. Acute undifferentiated leukemia in first or second remission.
  8. 4. Acute biphenotypic leukemia in first or second complete remission.
  9. 5. Chronic myelogenous leukemia in either chronic or accelerated phase.
  10. 6. One of the following myelodysplastic syndrome(s) defined by the following:
  11. 5. Receiving myeloablative or reduced-intensity conditioning regimens.
  12. 6. Adequate renal and hepatic function prior to initiation of conditioning regimen, therefore between 40 days prior and 10 days prior to BMT, documented as follows:
  13. 1. Hepatic: alanine aminotransferase less than or equal to (≤) 2.5 × upper limit of normal (ULN) and total serum bilirubin ≤1.5 × ULN (excluding Gilbert's Syndrome).
  14. 2. Renal: serum creatinine ≤2 milligrams (mg)/deciliter (dL) and with creatinine clearance (CrCl) greater than or equal to (≥) 30 milliliters (mL)/minute (min) without a history of renal transplant, or undergoing weekly dialysis within 4 weeks of the BMT.
  15. 7. Baseline blood samples drawn for Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 15 days before randomization, with results available prior to randomization.
  16. 8. Baseline Toxoplasma serologies available within 6 weeks prior to randomization. Subjects with a positive toxoplasma IgG serology at any time prior to randomization do not need to repeat the toxoplasma serologies (IgG and IgM) and will be considered to have a prior history of toxoplasmosis.
  17. 9. Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency determination by the investigator prior to randomization with no known evidence of G6PD deficiency performed any time prior to randomization. If the Investigator assesses the subject as G6PD sufficient, the G6PD test result does not need to be entered into the EDC system.
  18. 10. Female subjects of child-bearing potential \<2 years post-menopausal (unless surgically sterile) must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence (only possible if it corresponds to the subject's usual lifestyle) while participating in this study, and for 30 days after the last dose of study drug. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.
  1. 1. Diagnosis of AML not in morphological remission.
  2. 2. Diagnosis of chemotherapy-resistant lymphoma: a first relapse can occur provided that a second complete remission has occurred.
  3. 3. Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of randomisation.
  4. 4. Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤50%, or shortening fraction ≤26%.
  5. 5. Personal or family history of Long QT interval on electrocardiogram (ECG) (QT) syndrome or a prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) (\>470 milliseconds \[msec\] in males and \>480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, quinidine, or halofantrine.
  6. 6. Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin) or forced expiratory volume in 1 second (FEV1) ≤65% of predicted value, or O2 saturation ≤82% on room air.
  7. 7. Suspected or documented PCP within 2 years of screening.
  8. 8. Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (Fungitell ≥80 picograms \[pg\]/mL or Fujifilm Wako \>11 pg/mL) within 15 days prior to the transplant.
  9. 9. Receipt of previous allogeneic BMT.
  10. 10. Planned receipt of cord blood for transplantation.
  11. 11. Planned peripheral blood or marrow autograft.
  12. 12. Not applicable to protocol Amendment 6.
  13. 13. Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  14. 14. History of severe (Grade ≥3) ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
  15. 15. . .
  16. 1. Planned or ongoing intake at screening of a known severe neurotoxic medication or with a known moderate neurotoxic medication in a patient with ataxia, tremor, motor neuropathy, or sensory neuropathy of CTCAE version 5.0 Grade 1 or higher.
  17. 2. Any contraindication or a medication or supplement known to severely interact with the standard antimicrobial regimen (SAR) as detailed in the US Prescribing Information (USPI) or Summary of Product Characteristics (SmPC) of fluconazole, posaconazole, or TMP/SMX.
  18. 16. Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
  19. 17. Known hypersensitivity or inability to receive TMP/SMX or any of its excipients, including but not limited to anaphylaxis, exfoliative skin disorders, or acute porphyria.
  20. 18. Recent use of an investigational medicinal product within 28 days or 5 half-lives of the investigational medicinal product, whichever is greater, to prevent overlapping toxicities when this study's investigational product is dosed, or presence of an investigational device at the time of screening. In some cases, use of investigational products may be acceptable in consultation with the Sponsor's Medical Monitor.
  21. 19. Known infection with HIV. Subjects with unknown HIV status should be tested for HIV antibodies per standard of care.
  22. 20. Pregnant or lactating females.
  23. 21. The Principal Investigator (PI) determines that the subject should not participate in the study.
  24. 22. Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).
  25. 23. Known liver cirrhosis, diagnosed according to country or Medical Society specific guidelines and documented in the medical records prior to initiating conditioning regimen.

Contacts and Locations

Study Contact

Head of Clinical Operations
CONTACT
00441223424444
terry.nichols@mundipharma-rd.eu

Principal Investigator

Gu Lung Lin, MD
STUDY_DIRECTOR
Mundipharma Research Limited

Study Locations (Sites)

University of Alabama at Birmingham
Birmingham, Alabama, 35233
United States
UCLA Center for Health Sciences
Los Angeles, California, 90095
United States
Augusta University Medical Center
Augusta, Georgia, 30912
United States
Rush University Medical Center
Chicago, Illinois, 60612
United States
University of Chicago
Chicago, Illinois, 60637
United States
University of Maryland Medical Center
Baltimore, Maryland, 21201
United States
Massachusetts General Hospital
Boston, Massachusetts, 02114
United States
Mayo Clinic
Rochester, Minnesota, 55905
United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601
United States
Stony Brook University Hospital
Stony Brook, New York, 11794
United States
The University of Oklahoma College of Medicine
Oklahoma City, Oklahoma, 73104
United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98108
United States

Collaborators and Investigators

Sponsor: Mundipharma Research Limited

  • Gu Lung Lin, MD, STUDY_DIRECTOR, Mundipharma Research Limited

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-05-11
Study Completion Date2025-12

Study Record Updates

Study Start Date2020-05-11
Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

  • Mycoses
  • Prophylaxis of Invasive Fungal Infections
  • Aspergillus
  • Candidiasis
  • Candidemia
  • Candidiasis, Invasive
  • Fungemia
  • Sepsis
  • Blood and Marrow Transplant (BMT)
  • Infection
  • Invasive Fungal Infections
  • Systemic Inflammatory Response Syndrome
  • Inflammation
  • Pathologic Processes
  • Fluconazole
  • Posaconazole
  • Caspofungin
  • Trimethoprim-sulfamethoxazole (TMP/SMX)
  • Echinocandins
  • Antifungal Agents
  • 14-alpha Demethylase Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Molecular Mechanisms of Pharmacological Action
  • Steroid Synthesis Inhibitors
  • Physiological Effects of Drugs
  • Cytochrome P-450 CYP2C9 Inhibitors
  • Cytochrome P-450 CYP2C19 Inhibitors
  • Pneumocystis
  • Mold Infection
  • Rezafungin
  • Anti-Infective Agents

Additional Relevant MeSH Terms

  • Candidemia
  • Mycoses
  • Fungal Infection
  • Fungemia
  • Invasive Candidiasis
  • Pneumocystis
  • Mold Infection
  • Invasive Fungal Disease
  • Prophylaxis of Invasive Fungal Infections
  • Aspergillus