Standard Therapy Using Tacrolimus, Mycophenolate Mofetil and Prednisone For Chronic Lung Transplant Rejection (BOS)

NCT04415476 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HP-00091412
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone (S) compared to standard therapy (tacrolimus, mycophenolate mofetil (MMF) and prednisone) (ST) for chronic rejection, defined as grades 1 and 2 bronchiolitis obliterans syndrome (BOS); BOS defined as ≥ 20% decline from maximal post-transplant FEV1.

Conditions

Disorder Related to Lung Transplantation; Chronic Rejection of Lung Transplant; Decreased Immunologic Activity

Keywords

lung function; Lung Transplantation; case-control study; bronchiolitis obliterans syndrome (BOS)

Outcome Measures

Primary Outcomes (3)

• Death

  Increase in motility

  2 years

• Re-Transplantation

  Increase in re-transplantation from baseline

  2 years

• FEV1 (Forced Respiratory Volume in 1 second)

  Greater or equal to 20% decline in FEV1 from randomization

  2 years

Secondary Outcomes (2)

• FVC (Forced Vital Capacity)

  2 years

• FEF (forced expiratory flow)

  2 years

Study Arms (2)

Sirolimus and Tacrolimus and prednisone

OTHER

Assigned Interventions Sirolimus (Rapamune) Tacrolimus (Prograft) Prednisone (Deltasone, Prednicot, Rayos, Sterapred)

Drug: Assigned Interventions

Standard of Care

EXPERIMENTAL

Arm1:) sirolimus and tacrolimus and prednisone group: Tacrolimus, The patient will receive 0.1-0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 5-12 ng/ml. Mycophenolate mofetil (NA )Stopped upon sirolimus initiation Sirolimus:1-5 mg/day PO if \>40 kg / 1 mg/m²/day if \<40 kg trough blood levels 5-12 ng/ml Prednisone:20 mg/day PO if \>40 kg and 10 mg/day if \<40 kg, adjust based on adverse effects. Arm 2) Standard Therapy Tacrolimus:0.1 to 0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 8-12 ng/ml Mycophenolate mofetil:750-1250 mg bid PO and adjust to tolerance (WBCs and GI side effects Sirolimus: NA Prednisone: Prednisone dose 20 mg/day PO if \>40 kg and 10 mg/day if \<40 kg, adjust based on adverse effect

Drug: Assigned Interventions

Interventions

Assigned Interventions DRUG

This is a prospective single-center, open-label, randomized, controlled pilot study in the treatment of chronic rejection (CR), defined as grade 1 and 2 BOS, in adult recipients of a pulmonary allograft (single or double lungs). Patients meeting entry criteria shall demonstrate a sustained decline in FEV1 having met stage 1 or 2 BOS. Patients randomized to the study arm, will be treated with Sirolimus (S) orally in place of MMF in addition to tacrolimus and prednisone compared to those patients randomized to defined ST alone (tacrolimus, MMF and prednisone). The trial duration will be approximately 2 years for each subject randomized. Treatment compliance and safety will be monitored by clinic visits at 4-6 week intervals for the 2 year subject duration and will include standard physical examinations and monitoring of routine clinical and laboratory parameters including cause of hospitalizations and rate of adverse events including death in each group. T

Also known as: Tacrolimus, Mycophenolate mofetil, Prednisone, Sirolimus, Prograft, Cellcept, Deltasone, Prednicot, Rayos, Sterapred, Rapamune

Sirolimus and Tacrolimus and prednisone; Standard of Care

Eligibility Criteria

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

You may qualify if:

• Age: 18 or older.
• Recipient of a single or double pulmonary allograft at least twelve months before study entry.
• Clinically diagnosed BOS grade 1 or 2
• Receiving oral TAC-based immunosuppression according to institutional standards.
• Capable of understanding the purposes and risks of the study, has given written informed consent and agrees to comply with the study requirements and capable of protocol adherence.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry.
• Stable to enable routine pre and post-transplant bronchoscopy with BAL and biopsy.
• Fasting cholesterol \< 250 mg/dL, fasting triglycerides \< 250 mg/dL -

You may not qualify if:

• Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry.
• Mechanical ventilation.
• At screening FEV1 \< 1 liter and/or \< FEV1 of 25 % predicted.
• Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy.
• Women who breastfeed.
• Known hypersensitivity to sirolimus.
• Serum creatinine value of \> 2.5 mg/dL or chronic dialysis use or liver disease with a bilirubin \> 2 mg/dL.
• Subjects with severe underlying disease other than BOS that is thought to become fatal within four months of clinical assessment.
• Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to study entry. This is defined as any treatment that is implemented under an Investigational New Drug.
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
• Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial.
• Clinically significant bronchial strictures unresponsive to dilatation procedures.
• Subjects with malignancy diagnosed within one year prior to screen (with the exception of skin cancers).
• Lipid panel fasting cholesterol \> 250 mg/dL, fasting triglycerides \>250 mg/dL

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Related Publications (1)

• Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.

  PMID: 16407509 RESULT

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Tacrolimus; Mycophenolic Acid; Prednisone; Sirolimus

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Aldo T Iacono, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Paralled Assignment

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: June 4, 2020
• Study Start: June 30, 2020
• Primary Completion: June 30, 2024
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 6, 2023

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share