Inhalations of Ultra-low Doses of Melphalan for the Treatment of Non-cystic Fibrosis Bronchiectasis

NCT04278040 | Unknown Phase 2

• 1 other identifier: PSRI02-18
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This non-randomised open-label prospective pilot study evaluates the safety and efficacy of inhalations of ultra-low doses of alkylating drug melphalan for the treatment of non-cystic fibrosis bronchiectasis. All patients will receive 0,1 mg of melphalan in 5 daily inhalations 1 time per day.

Conditions

Non-cystic Fibrosis Bronchiectasis

Keywords

bronchiectasis; treatment; inhalation; low doses; alkylating drugs

Outcome Measures

Primary Outcomes (1)

• Frequency of drug-related side effects.

  The evaluation of side-effects, typical for the conventional therapeutic doses of melphalan (cough, bronchospasm, pulmonary fibrosis, interstitial pneumonitis; anorexia, gastrointestinal bleeding, ulcers of the stomach and duodenum, stomatitis, nausea, vomiting, esophagitis, diarrhea; myelodepression (leukopenia, thrombocytopenia, anemia), hemolytic anemia, bleeding and hemorrhage, vasculitis, veno-occlusive lesions, asystole; impaired urination, hematuria, hyperuricemia, nephropathy, edema, proteinuria, ovarian hypofunction, amenorrhea, azoospermia; anaphylaxis, anaphylactic shock, Quincke's edema, urticaria, skin rash, itching; dysfunction of the central nervous system, pain (back, side pain), the development of infections, fever, chills, alopecia, an increase in the concentration of 5-hydroxyindoleacetic acid, necrosis of the perivascular space, a feeling of heat and / or tingling at the injection site)

  6 months from the first inhalation

Secondary Outcomes (2)

• The changes of The St George's Respiratory Questionnaire (SGRQ)

  Day1 - Day 177 (±7 days)

• The changes of The Quality of Life-Bronchiectasis (QOL-B) questionnaire

  Day1 - Day 177 (±7 days)

Study Arms (1)

Non-cystic fibrosis bronchiectasis (NCFB) patients

EXPERIMENTAL

Inhalations with Melphalan 0,1 mg dissolved in 2 ml sodium chloride (NaCl) 0,9% 1 per day for 5 consequent days

Drug: Melphalan

Interventions

Melphalan DRUG

Inhalations with low doses of Melphalan for 5 consequent days

Also known as: Alkeran

Non-cystic fibrosis bronchiectasis (NCFB) patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Established diagnosis witn CT scan of non-cystic fibrosis bronchiectasis more than 12 months before the screening visit.
• Sputum expectoration not less than 3 months per year during more than 2 consecutive years
• Willing of the patient for cooperation
• Pregnant and lactating women and all women who are physiologically capable of becoming pregnant, who do not agree to use one or more of the following effective methods of contraception: intrauterine device or intrauterine system; hormonal contraception (implantable and oral preparations, patches); barrier methods of contraception; male sterilization (with appropriate documentation after a vasectomy about the absence of sperm in the ejaculate).
• Effective contraception is used throughout the study until the last visit. "True abstinence" is acceptable only if it corresponds to the patient's preferred and habitual way of life.
• Postmenopausal women (physiological menopause is defined as "no menstruation for 12 consecutive months") and women who have undergone sterilization surgery (for example, tubal occlusion, hysterectomy or bilateral salpingectomy) can be included in the study.
• A history of cystic fibrosis.
• Any exacerbation of respiratory infection requiring the use of systemic corticosteroids and / or antibiotics or hospitalization, which developed after the signing of the informed consent form and before the randomization visit (day 1, start of treatment). The criterion should be specified during the randomization visit.
• The presence of diseases of the respiratory tract, in addition to bronchiectasis, which can affect the effectiveness of the study drug and patient safety. Such conditions may include, among others, active tuberculosis, lung cancer, sarcoidosis, chronic obstructive pulmonary disease (COPD) IV (GOLD, 2017), uncontrolled bronchial asthma with respiratory failure, high pulmonary hypertension (\> 25 mm Hg), interstitial lung disease, etc.
• Patients with a clinical significant disease of the cardiovascular system (for example, unstable angina, chronic heart failure New York Heart Association (NYHA) III / IV, acute myocardial infarction (within 6 months before inhalation of 1 dose), etc.
• Atrial fibrillation patients.
• Clinical significant 12-lead ECG abnormalities that may affect patient safety. The corrected QT interval (QTc) interval on the electrocardiogram (ECG in 12 leads) is more than 450 ms for men and more than 470 ms for women on screening and randomization visits.
• A history of hypersensitivity to any of the substances used in the study.
• Clinically significant deviations of laboratory parameters, indicating a significant or unstable concomitant disease, which may affect the effectiveness of the study drug or patient safety.

You may not qualify if:

• Informed consent withdrawn by the patient.
• The patient doesn't follow the instructions of the research staff regarding the requirements of the research protocol.
• Unable to contact patient.
• The researcher believes that participation in the study is not in the interests of the patient and / or further participation in the study is unsafe for the patient's health.
• The patient has developed adverse event, which, according to the researcher, makes further participation in the study unsafe for the patient.
• The licensing authority or ethics committee, for any reason, decides to discontinue the entire study or close this research center.
• A female patient becomes pregnant, is planning a pregnancy, or is breastfeeding while participating in this study.

Sponsors & Collaborators

• Federal State Budgetary Institution, Pulmonology Scientific Research Institute: lead
• Moscow State University of Medicine and Dentistry: collaborator

Study Sites (1)

Kirill Zykov

Moscow, 115682, Russia

RECRUITING

Related Publications (8)

• Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Canton R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaro J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3):1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep.

  PMID: 28889110 BACKGROUND

• Pukhalsky AL, Shmarina GV. Stimulatory and protective effects of alkylating agents applied in ultra-low concentrations. Pharmacology. 2001;62(3):129-32. doi: 10.1159/000056084.

  PMID: 11287812 BACKGROUND

• Shmarina G, Pukhalsky A, Alioshkin V, Sabelnikov A. Melphalan reduces the severity of experimental colitis in mice by blocking tumor necrosis factor-alpha signaling pathway. Ann N Y Acad Sci. 2007 Jan;1096:97-105. doi: 10.1196/annals.1397.075.

  PMID: 17405921 BACKGROUND

• Pukhalsky A, Shmarina G, Alioshkin V, Sabelnikov A. Alkylating drugs applied in non-cytotoxic doses as a novel compounds targeting inflammatory signal pathway. Biochem Pharmacol. 2006 Nov 30;72(11):1432-8. doi: 10.1016/j.bcp.2006.03.008. Epub 2006 Mar 14.

  PMID: 16620792 BACKGROUND

• Pukhal'skii AL, Shmarina GV, Zykov KA, Aleshkin VA. [Effect of steroid therapy on the clinical course of bronchial asthma]. Vestn Ross Akad Med Nauk. 2009;(6):3-9. Russian.

  PMID: 19645099 BACKGROUND

• Martinez-Garcia MA, Maiz L, Olveira C, Giron RM, de la Rosa D, Blanco M, Canton R, Vendrell M, Polverino E, de Gracia J, Prados C. Spanish Guidelines on the Evaluation and Diagnosis of Bronchiectasis in Adults. Arch Bronconeumol (Engl Ed). 2018 Feb;54(2):79-87. doi: 10.1016/j.arbres.2017.07.015. Epub 2017 Nov 9. English, Spanish.

  PMID: 29128130 BACKGROUND

• Sinitsyn EA., Zykov KA. Non-cystic Fibrosis Bronchiectasis: Actual Problem Review and Treatment Prospects. Journal of Clinical Practice.2018;9(4):55-64. doi: https://doi.org/10.17816/clinpract9455-64

  BACKGROUND

• Chalmers JD, Chotirmall SH. Bronchiectasis: new therapies and new perspectives. Lancet Respir Med. 2018 Sep;6(9):715-726. doi: 10.1016/S2213-2600(18)30053-5. Epub 2018 Feb 23.

  PMID: 29478908 BACKGROUND

MeSH Terms

Conditions

Bronchiectasis; Respiratory Aspiration

Interventions

Melphalan

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kirill Zykov, Prof

  Federal State Budgetary Institution, Pulmonology Scientific Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evgeny Sinitsyn

CONTACT

+79269490744; sinymlad@list.ru

Kirill Zykov, Prof

CONTACT

+79257729462; kirillaz@inbox.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: The trial was open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director for Science and Innovations

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 20, 2020
• Study Start: June 20, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 30, 2021
• Last Updated: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)