Acute Lymphoid Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Non-Hodgkin Lymphoma
Conditions
Keywords
multiple myeloma [MM], non-Hodgkin lymphoma [NHL], acute myeloid leukemia [AML], acute lymphoid leukemia [ALL], chronic myeloid leukemia [CML]
Brief summary
To determine the maximum tolerated dose (MTD) of OPB-51602
Interventions
DRUGOPB-51602
once daily during the treatment period
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with a confirmed diagnosis of MM, NHL, AML, ALL or CML. 2. Patients who are responsive or have relapsed following standard treatment 3. Patients capable of providing written informed consent 4. Japanese patients age 20 to 75 years (inclusive) at time of informed consent 5. ECOG performance status score of 0-1 6. Life expectancy of at least 3 months 7. Adequate vital organ function 8. Patients who, together with their partner, are willing and capable of using an appropriate method of contraception throughout the trial period and until at least 12 weeks after final IMP administration
Exclusion criteria
1. Patients with other primary malignant tumors 2. Symptomatic CNS involvement 3. Ongoing or active infection, or complication that is not controllable by medication or other means 4. Complication of uncontrolled cardiac disease 5. Female patients who are pregnant, possibly pregnant, or lactating, or who wish to become pregnant during the study period 6. Patients who have received another study drug, or who have received chemotherapy, immunotherapy, cytokine therapy, surgery, or radiotherapy for treatment of the primary disease, within 4 weeks prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Treatment Emergent Adverse Events | From first study medication to on Day 31 (after repeated 28 days medication from Day 4 to 31) | Treatment emergent adverse events observed during outcome measure time frame. A Treatment Emergent Adverse Event was defined as an AE occurring after the start of IMP administration. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | From first study medication to on Day 31 (after repeated 28 days medication from Day 4 to 31) | DLT was defined as adverse events occurring during Cycle 1 and: (1) Grade 3 or higher nausea, vomiting, or diarrhea despite the use of anti-emetic or antidiarrheal drugs, (2) Grade 3 or higher non-hematologic toxicity, excluding alopecia, (3) AEs requiring interruption of the IMP for a total of 8 days or longer, (4) Grade 4 neutropenia lasting ≥ 8 days (not applicable for leukemia), (5) Grade 3 or higher febrile neutropenia or infection due to neutropenia (not applicable for leukemia), (6) Grade 4 thrombocytopenia or Grade 3 thrombocytopenia requiring platelet transfusion (not applicable for leukemia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response | From first dose of study medication to withdrawal examination | Assessment of the treatment response was evaluated according to internationally recognized response criteria for multiple myeloma, non-Hodgkin's lymphoma, acute myeloid leukemia, chronic myeloid leukemia. Response was defined as at least partial response or partial remission (PR) according to the criteria for efficacy assessment. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPB-51602 OPB-51602: 1, 2, 3, 4 and 6 mg/day oral once daily (QD) in a 4 week cycle
OPB-51602: once daily during the treatment period | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Definite progression of primary disease | 1 | 0 | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | OPB-51602 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 6.5 |
| Region of Enrollment Japan | 20 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 4 / 4 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 2 / 4 | 0 / 6 | 0 / 3 |
Outcome results
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLT was defined as adverse events occurring during Cycle 1 and: (1) Grade 3 or higher nausea, vomiting, or diarrhea despite the use of anti-emetic or antidiarrheal drugs, (2) Grade 3 or higher non-hematologic toxicity, excluding alopecia, (3) AEs requiring interruption of the IMP for a total of 8 days or longer, (4) Grade 4 neutropenia lasting ≥ 8 days (not applicable for leukemia), (5) Grade 3 or higher febrile neutropenia or infection due to neutropenia (not applicable for leukemia), (6) Grade 4 thrombocytopenia or Grade 3 thrombocytopenia requiring platelet transfusion (not applicable for leukemia).
Time frame: From first study medication to on Day 31 (after repeated 28 days medication from Day 4 to 31)
Population: DLT evaluated subjects who had achieved ≧75% study drug compliance during a 4-week (28-day) treatment period starting from Day 4. No statistical analysis provided for Subjects With DLTs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPB-51602 | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-51602 2mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-51602 3mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-51602 4mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 participants |
| OPB-51602 6mg/Day | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 participants |
Primary
Subjects With Treatment Emergent Adverse Events
Treatment emergent adverse events observed during outcome measure time frame. A Treatment Emergent Adverse Event was defined as an AE occurring after the start of IMP administration.
Time frame: From first study medication to on Day 31 (after repeated 28 days medication from Day 4 to 31)
Population: Safety population No statistical analysis provided for Subjects With Treatment Emergent Adverse Events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPB-51602 | Subjects With Treatment Emergent Adverse Events | 20 participants |
Secondary
Treatment Response
Assessment of the treatment response was evaluated according to internationally recognized response criteria for multiple myeloma, non-Hodgkin's lymphoma, acute myeloid leukemia, chronic myeloid leukemia. Response was defined as at least partial response or partial remission (PR) according to the criteria for efficacy assessment.
Time frame: From first dose of study medication to withdrawal examination
Population: Efficacy population included all treated subjects who had received at least 1 dose of study drug.~No statistical analysis provided for treatment response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPB-51602 | Treatment Response | 0 participants |