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Pirfenidone after Stem Cell Transplant in Treating Participants with Bronchiolitis Obliterans Syndrome

Trial Status: Active

This phase I trial studies the side effects of pirfenidone after stem cell transplant in treating participants with bronchiolitis obliterans syndrome. Pirfenidone is an anti-inflammatory and antifibrotic agent that may slow the growth of tumor cells.

Inclusion Criteria

  • Clinical symptoms (e.g., dyspnea or cough) consistent with BOS of ≥ 2 months duration
  • Presence of chronic graft versus host disease (cGVHD) in an organ other than lung
  • Subjects must have had recent pulmonary function test (PFT) measured for at least 3 months prior to study enrollment that show: * A decrease in % forced vital capacity (FVC) and/or % forced expiratory volume in 1 second (FEV1) ≥ 20% at screening compared with pre-transplant baseline * Bronchodilator response on PFT testing that results in an FEV1 < 75%
  • Diagnosis of BOS by one of the following criteria * Transbronchial or surgical lung biopsy demonstrating the obliterative bronchiolitis lesion * Volumetric computed tomography (CT) scan with lung density analysis with ≥ 28% air trapping * National Institutes of Health (NIH)-based PFT criteria for the diagnosis of BOS: FEV1/FVC < 0.7 and FEV1 < 75% * Evidence of clinical improvement after treatment for BOS initiated
  • No features supporting an alternative diagnosis by transbronchial biopsy, bronchoalveolar lavage (BAL), surgical lung biopsy, culture and non-culture based data, if performed
  • Total bilirubin below the upper limit of normal (ULN), excluding patients with Gilbert’s syndrome
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 3 × ULN
  • Alkaline phosphatase < 2.5 × ULN
  • Creatinine clearance (CrCl) > 30 mL/min, calculated using the Cockcroft-Gault formula
  • Cardiac electrophysiologic stability as defined by an electrocardiogram (ECG) with a corrected QT (QTc) interval < 500 msec at screening
  • White blood cell count > 3 K/uL
  • Absolute neutrophil count > 1.5 K/uL
  • Platelet count > 20 K/uL
  • Multiple immune suppressive medications are routinely used in patients after HCT with cGVHD and will be allowed to continue while participating in this study; these concomitant medications include but are not limited to: tacrolimus, sirolimus, ibrutinib, corticosteroids, mycophenolate mofetil, ruxolitinib, vismodegib, cyclosporine, montelukast, azithromycin, corticosteroids inhalers including those with a long acting beta-agonist (e.g., salmeterol); additional medications and therapies (e.g., extracorporeal photophoresis) for the intentional treatment of BOS will be permitted at the discretion of the provider; prophylactic antimicrobials including trimethoprim/sulfamethoxazole, azole class of antifungals, and acyclovir will also be allowed
  • There are no gender or race-ethnicity-based restrictions
  • Patients must have life-expectancies > 6 months to be included in the trial
  • Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status will not be employed
  • Participants must be able to understand and sign a written informed consent form and understand the importance of adherence to study treatment and protocol; in addition, participants must demonstrate a willingness to follow all study requirements, including the concomitant medication restrictions, throughout the study

Exclusion Criteria

  • Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the liver as manifested by rising liver function tests (LFTs) prior to initiation of study treatment
  • Uncontrolled infection
  • Major surgery within the past 2 months
  • The use of another investigational drug within the previous 30 days
  • Inability to attend scheduled clinic visits
  • Inability to perform PFTs
  • Significant clinical change in health in the past 30 days
  • Body mass index (BMI) < 17.5
  • Life expectancy =< 6 months due to any condition other than BOS that, in the opinion of the investigator, is likely to result in the death of the patient
  • History of unstable or deteriorating cardiac or pulmonary disease (other than BOS) within the previous 6 months, including but not limited to the following: * Unstable angina pectoris or myocardial infarction * Congestive heart failure requiring hospitalization * Uncontrolled clinically significant arrhythmias
  • Pregnancy or lactation
  • Family or personal history of long QT syndrome
  • There are no specific restrictions for therapies to treat cGVHD
  • Investigational therapy, defined as any drug that has not been approved for marketing for any indication in cGVHD will be restricted from the study
  • Participants with prior use of pirfenidone or known hypersensitivity to any of the components of study treatment will be excluded from the study
  • The following medications may significantly increase the level of pirfenidone and should not be taken concurrently including: fluvoxamine, ciprofloxacin > 500 mg twice daily, systemically administered aminolevulinic acid, vemurafenib and enoxacin, any other strong inhibitors of P450 isozymes CYP1A2, CYP2C9, 2C19, 2D6, and 2E1 should be avoided
  • Participants that cannot take alternate medications will be excluded from this study
  • Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study; if abstinence is not practiced, one of the two methods of birth control should be an oral contraceptive (e.g., oral contraceptive and a spermicide)
  • Participants that are cancer survivors or those with human immunodeficiency virus (HIV) will not be excluded from the study


Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
Contact: Joseph Hsu
Phone: 650-725-9536


I. To assess the tolerability of pirfenidone in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT).


I. To assess the safety of treatment with pirfenidone in patients with BOS after HCT and to conduct an exploratory analysis of treatment efficacy.

OUTLINE: This is a dose-escalation study.

Participants receive pirfenidone orally (PO) thrice daily (TID) for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 28 days.

Trial Phase Phase I

Trial Type Supportive care

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Joseph Hsu

  • Primary ID VAR0158
  • Secondary IDs NCI-2018-00429
  • ID NCT03315741