Trial Title:
Evaluate the Safety and Efficacy for Oral Mucositis Prevention of MIT-001 in Auto HSCT
NCT ID:
NCT05493800
Condition:
Oral Mucositis
Lymphoma
Multiple Myeloma
Hematologic Cancer
Conditions: Official terms:
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Mucositis
Stomatitis
Conditions: Keywords:
oral mucositis
MIT-001
auto HSCT
HSCT
hematopoietic stem cell transplantation
ferroptosis inhibitor
necrosis inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Part I: open label
Part II: double blind, randomized, and Placebo controlled
Intervention:
Intervention type:
Drug
Intervention name:
MIT-001
Description:
Corresponding dose of MIT-001 IV injection during 0.5~1hr
Arm group label:
Part 1, MIT-001 10 mg group
Arm group label:
Part 1, MIT-001 20 mg group
Arm group label:
Part 1, MIT-001 30 mg group
Arm group label:
Part 1, MIT-001 5 mg group
Arm group label:
Part 2, 20mg of MIT-001 high dose group
Arm group label:
Part 2, 5mg of MIT-001 low dose group
Intervention type:
Drug
Intervention name:
normal saline
Description:
normal saline IV injection
Arm group label:
Part 2, placebo(normal saline) group
Other name:
placebo
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).
Detailed description:
In Part 1, it was to determine Recommended Part 2 Dose(RP2D) the prevention effect of
MIT-001 in combination with conditioning regimen in autologous hematopoietic stem cell
transplantation(auto-HSCT) and to evaluate the pharmacokinetic characteristics of
MIT-001.
In Part 2, it's to determine the optimal dose of MIT-001 in combination with conditioning
regimen in auto-HSCT.
This clinical trial consists of a 28-days of screening period, 4 to 9 days of
conditioning chemotherapy with MIT-001 treatment, auto-HSCT and a 14-days of follow-up
and recovery period.
MIT-001 group consists of 5 mg (group 1), 10 mg (group 2), and 20mg (group 3), and the
subject will be assigned to from 5 mg of MIT-001 sequentially.
After completion of MIT-001 administration from all 3 MIT-001 groups, Steering Committee
(SC) was convened and reviewed the safety and efficacy to determine one of the
followings.
- Determine whether the next dose (Group 4: 30 mg) in Part 1: It was not proceeded.
- Determine the RP2D to enter Part 2 phase: 5mg as low dose, 20mg as high dose for
Part 2 The investigators will continuously monitor the safety of MIT-001, and can
request the steering committee call at any time, and can be carefully reviewed the
data such as safety and efficacy.
In Part 2, the subjects are randomly assigned to either one of MIT-001 treatment groups
(high-dose, low-dose among RP2D) and placebo at a ratio of 1: 1: 1. If two or more
conditioning regimen are determined, conditioning regimen can be considered the
stratification factor. Subject will be randomly assigned to either group in blinded
method.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men and women aged 19 to 70 years old
2. 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.)
3. Patients who have not received a hematopoietic stem cell transplant before
4. Patients with Body Mass Index (BMI) 35 or less
5. Patients who have prepared at least 2 x 10^6 CD34+ cell/kg
6. Patients whose hematologic, kidney and liver functions were confirmed to be proper
through the following laboratory test results last measured within 8 days prior to
the investigational product(IP) administration Laboratory endpoint Required limit
for inclusion Absolute neutrophil count (ANC) ≥ 1,000/mm^3 Hemoglobin (Hb) ≥ 9.0
g/dL Platelet count ≥ 100,000/mm^3 Total bilirubin (TB) ≤ 2 mg/Dl AST and ALT ≤ 3.0
x ULN(if liver metastasis, ≤ 5 x ULN) Prothrombin time (PT) INR ≤ 1.5 (if taking
warfarin, < 3) Serum creatinine or creatinine clearance (CrCl) < 2 mg/dL or≥ 60
mL/min
7. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0
or 1
8. 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
Exclusion Criteria:
1. 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
2. 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
3. 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.)
4. Patients who participated in other clinical trials within 30 days from the start of
IP administration and received other study drug (or medical devices)
5. Patient who are judged to be difficult to participate in the study according to the
opinions of investigators
Gender:
All
Minimum age:
19 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Seoul ST. Mary's Hospital
Address:
City:
Seoul
Zip:
06591
Country:
Korea, Republic of
Facility:
Name:
Yeouido ST. Mary's Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Start date:
February 1, 2022
Completion date:
December 30, 2024
Lead sponsor:
Agency:
MitoImmune Therapeutics
Agency class:
Industry
Source:
MitoImmune Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05493800
