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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
60
Corresponding dose of MIT-001 IV injection during 0.5\~1hr
normal saline IV injection
Seoul ST. Mary's Hospital
Seoul, South Korea
Yeouido ST. Mary's Hospital
Seoul, South Korea
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)
Time frame: up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)
The incidence of oral mucositis by WHO OM grading scale
① Grade 1 or higher, ② Grade 2 or higher, ③ Grade 4 or higher 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)
Time frame: 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
① Grade 1 ② Grade 2 ③ Grade 3 ④ Grade 4 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)
Time frame: 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
The average grade of each point 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)
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Time frame: Each 1, 5, 7, 14, 21 and 28 day after the end of therapy
The duration of oral mucositis by WHO OM grading scale
① Grade 2 or higher, ② Grade 3 or higher, ③ Grade 4 or higher 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)
Time frame: 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
① Grade 1 or higher, ② Grade 2 or higher, ③ Grade 3 or higher, ④ Grade 4 or higher Grade 0 = Normal Grade 1 = Asymptomatic or mild symptoms; intervention not indicated Grade 2 = Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated Grade 3 = Severe pain; interfering with oral intake Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death
Time frame: up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)
The average grade of oral mucositis by NCI-CTCAE v5.0 criteria
The average grade of each point Grade 0 = Normal Grade 1 = Asymptomatic or mild symptoms; intervention not indicated Grade 2 = Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated Grade 3 = Severe pain; interfering with oral intake Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death
Time frame: Each 1, 5, 7, 14, 21 and 28 day after the end of therapy
The mean area under curve(AUC) of score for each question in oral mucositis daily questionnaire(OMDQ)
Q1: General health condition scale: 0(worst possible) to 10(perfect health) Q2: Mouth and throat pain: 0(no soreness) to 4(extreme soreness) Q3: Salvia swallowing, drinking water, eat rice, speaking ans sleeping: 0(no soreness) to 4(extreme soreness) Q4: General mouth and throat pain: 0(no soreness) to 10(worst possible)
Time frame: up to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)
The proportion of using opioid analgesics
The proportion of patients who used opioid analgesics up to 14 days after the end of therapy.
Time frame: From the baseline to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)
Total cumulative dose of opioid analgesics
It will be calculated as morphine equivalents dose
Time frame: From the baseline to 14 days after the end of therapy( or discharge if hospitalization extension is necessary)