Evaluate the Safety and Efficacy for Oral Mucositis Prevention of MIT-001 in Auto HSCT

NCT05493800 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MIT001-OM-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Evaluate the efficacy and safety for the prevention of oral mucositis and PK of MIT-001 for lymphoma or multiple myeloma patients receiving conditioning chemotherapy for autologous hematopoietic stem cell transplantation(auto-HSCT).

Conditions

Oral Mucositis; Lymphoma; Multiple Myeloma; Hematologic Cancer

Keywords

oral mucositis; MIT-001; auto HSCT; HSCT; hematopoietic stem cell transplantation; ferroptosis inhibitor; necrosis inhibitor

Outcome Measures

Primary Outcomes (1)

• The incidence of Severe Oral Mucositis(SOM).

  OM is evaluated using the World Health Organization (WHO) OM grading scale that uses a scale of 0 to 4. SOM is defined as a WHO score of greater than or equal to 3. OM grading scale Grade 0 = Normal Grade 1 = Erythema and Soreness Grade 2 = Ulceration but can eat solid foods Grade 3 = Ulceration,diet limited to liquid (due to mucositis) Grade 4 = Ulceration of severity that patient requires parenteral feeding (due to mucositis)

  up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)

Secondary Outcomes (9)

• The incidence of oral mucositis by WHO OM grading scale

  up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)

• The incidence of oral mucositis based on the maximum severity by WHO OM grading scale

  up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)

• The average grade of oral mucositis by WHO OM grading scale

  Each 1, 5, 7, 14, 21 and 28 day after the end of therapy

• The duration of oral mucositis by WHO OM grading scale

  up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)

• The incidence of oral mucositis by NCI-CTCAE v5.0 criteria

  up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)

Other Outcomes (2)

• Adverse Events(AEs)

  From baseline to 28 day after discharge

• Auto hematopoietic stem cell engraftment

  From auto-HSCT to 28 day

Study Arms (7)

Part 1, MIT-001 5 mg group

EXPERIMENTAL

Part 1, MIT-001 5 mg, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 5 subject were enrolled sequentially.

Drug: MIT-001

Part 1, MIT-001 10 mg group

EXPERIMENTAL

Part 1, MIT-001 10 mg, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 6 subjects were enrolled sequentially.

Drug: MIT-001

Part 1, MIT-001 20 mg group

EXPERIMENTAL

Part 1, MIT-001 20 mg, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 5 subjects were enrolled sequentially.

Drug: MIT-001

Part 1, MIT-001 30 mg group

EXPERIMENTAL

Part 1, MIT-001 30 mg, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. It was optional but did not ptoceed according to Steering committee's decision because low level of MIT-001 is enough to show the efficacy and safety of MIT-001.

Drug: MIT-001

Part 2, 5mg of MIT-001 low dose group

EXPERIMENTAL

Part 2, MIT-001 low dose, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 15 subject will be enrolled parallelly.

Drug: MIT-001

Part 2, 20mg of MIT-001 high dose group

EXPERIMENTAL

Part 2, MIT-001 high dose, once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 15 subject will be enrolled parallelly.

Drug: MIT-001

Part 2, placebo(normal saline) group

PLACEBO COMPARATOR

Part 2, placebo(normal saline), once a day IV administration for 30 minutes before conditioning regimen administration 0.5\~1 hr. 15 subject will be enrolled parallelly.

Drug: normal saline

Interventions

MIT-001 DRUG

Corresponding dose of MIT-001 IV injection during 0.5\~1hr

Part 1, MIT-001 10 mg group; Part 1, MIT-001 20 mg group; Part 1, MIT-001 30 mg group; Part 1, MIT-001 5 mg group; Part 2, 20mg of MIT-001 high dose group; Part 2, 5mg of MIT-001 low dose group

normal saline DRUG

normal saline IV injection

Also known as: placebo

Part 2, placebo(normal saline) group

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 19 to 70 years old
• Patients with lymphoma or multiple myeloma planned for receiving one of the following conditioning chemotherapy followed by autologous hematopoietic stem cell transplantation
• BuCyE Regimen: Busulfan (iv) 3.2 mg/kg (Day 1, Day 2, Day 3) + Etoposide (iv) 400 mg/m² (Day 3, Day 4) + Cyclophosphamide (iv) 50 mg/kg/Mesna (iv) 50 mg/kg (Day 5, Day 6), and autologous HSCT after 1 day rest after completion of 6 days of conditioning chemotherapy
• BMT Regimen: Busulfan (iv) 2.4 mg/kg (Day 1, Day 2, Day 3) + Melphalan (iv) 40 mg/m2 (Day 4, Day 5) + Thiotepa (iv) 200 mg/ m2 (Day 6, Day 7), and autologous HSCT after 1 day rest after completion of 7 days of conditioning chemotherapy
• Melphalan Regimen: Melphalan (iv) 100 mg/m2 (Day 1, Day 2), and autologous HSCT after 1 day rest after completion of 2 days of conditioning chemotherapy
• BuMel Regimen: Busulfan (iv) 3.2 mg/kg (Day 1, Day 2, Day 3) + Melphalan (iv) 140 mg/m2 (Day 4), and autologous HSCT after 1 day rest after completion of 4 days of conditioning chemotherapy (In part 2, BUCYE, BMT and MELPHALAN regimens are allowed.)
• Patients who have not received a hematopoietic stem cell transplant before
• Patients with Body Mass Index (BMI) 35 or less
• Patients who have prepared at least 2 x 10\^6 CD34+ cell/kg
• Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1
• Patients who voluntarily decided to participate in this study after being informed of the study information, and provided written consent to faithfully comply with the study requirements

You may not qualify if:

• Patients who has the following medical history or concomitant diseases at screening
• Patients with oral mucositis or oral ulcer at screening
• Patients who have severe infections or other uncontrolled active infectious diseases at screening that require administration of antibiotics, antibacterial agents, antifungal agents, antivirals, etc. (e.g., Human Immunodeficiency Virus positive, active hepatitis B or active hepatitis C, etc.) However, in case of administration of antiviral drugs in patients with hepatitis B or C infection, whose disease is controlled, the subjects can be enrolled.
• Patients who have major cardiovascular disease within 6 months before screening, which includes, but not limited to Severe heart disease (heart failure (NYHA class 3 and 4), acute coronary artery disease (unstable angina, acute myocardial infarction), clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter, or other clinically significant arrhythmia and peripheral vascular diseases confirmed by the investigator Hypertrophic obstructive cardiomyopathy, clinically significant heart valve disease or aortic disease
• Patients who are considered inappropriate to participate in the study because they have uncontrolled disease and have a comorbid disease that requires treatment by the investigator's judgement (e.g., blood coagulation disorder, bleeding disorder or bleeding diatheses, pulmonary function decline, decline in renal function, hypotension, hypertension, hepatitis, liver cirrhosis, etc)
• Patients who have major mental illness (e.g., depression, bipolar disorder, etc.) or a history of drug/alcohol abuse
• If the following therapy has been administered or received, or when the need for administration is expected
• The following therapies within 12 weeks before the baseline that may have a significant effect on the results of the study Palifermin Oral low-level laser therapy Oral cryotherapy Glutamine (parenteral, IV supplement of protein amino acids containing glutamic acid, not glutamine supplements, are permitted)
• Vaccination of yellow fever vaccine or other live attenuated vaccine within 4 weeks before the baseline
• Anti-cancer or radiation therapy\* within 3 weeks before the baseline (However, the use of Anti-cancer drugs for hematopoietic stem cell collection is permitted and subjects who have been irradiated with head and neck within the last 2 years are excluded.) (\*Radio(chemo)therapy, chemotherapy, targeted therapy (small molecule drugs, monoclonal antibodies), cancer immunotherapy (biological drugs), or hormone therapy, etc.)
• The following drugs that may affect the metabolism of IP from within 7 days before the baseline to the end of treatment (EOT) period Strong CYP3A4 inhibitors: boceprevir, citrus x paradisi, clarithromycin, cobicistat, conivaptan, delavirdine, diltiazem, idelalisib, indinavir, itraconazole, ketoconazole, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, lopinavir/ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, voriconazole Strong CYP3A4 inducers: avasimibe, carbamazepine, enzalutamide, fosphenytoin, hypericum perforatum, lumacaftor, methylphenobarbital, mitotane, phenobarbital, phenobarbital quinine, primidone, rifabutin, rifampicin, rifapentine OATP inhibitors: cyclosporin A, cyclosporine, estradiol-17β-glucuronide, estrone-3-sulfate, rifampicin, rifamycin SV, lopinavir/ritonavir
• Pregnant and lactating women or women or childbearing potential and men who have a pregnancy plan up to 30 days after the end of the IP administration or who do not intend to use appropriate contraception: ① Hormonal contraceptives, ② Implantation of an intrauterine device or intrauterine system, ③ Double blocking method with spermicide (both male condom and closed cap (contraceptive diaphragm or neck cap) are used), ④ Infertility procedures (e.g., vasectomy, bilateral tubal ligation, etc.)
• Patients who participated in other clinical trials within 30 days from the start of IP administration and received other study drug (or medical devices)
• Patient who are judged to be difficult to participate in the study according to the opinions of investigators

Sponsors & Collaborators

• MitoImmune Therapeutics: lead

Study Sites (2)

Seoul ST. Mary's Hospital

Seoul, 06591, South Korea

Location

Yeouido ST. Mary's Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomatitis; Lymphoma; Multiple Myeloma; Hematologic Neoplasms

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Seok-Goo Cho, MD, PhD

  Seoul St. Mary's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part I: open label Part II: double blind, randomized, and Placebo controlled
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 was completed with 16 patients and open label design to to evaluate the pharmacokinetic characteristics, efficacy, and safety of MIT-001 on prevention effect of MIT-001 in combination with conditioning regimen in auto-HSCT. 5mg as low dose and 20mg as high dose of MIT-001 were determined as RP2D through steering comittee and optional group of 30mg was not needed at Part 1 because low level of MIT-001 was enough to show efficacy and safety of MIT-001. In Part 2, it's to determine the optimal dose (recommended part 2 dose (RP2D)) of MIT-001 in combination with conditioning regimen in auto-HSCT.

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 9, 2022
• Study Start: February 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: December 30, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)