Japanese Phase 1 Study to Evaluate Tolerated Dose, Safety, and Efficacy of Pomalidomide in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
pomalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Must be ≥ 20 years of age at the time of signing the informed consent document
- The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
- Must be able to adhere to the study visit schedule and other protocol requirements
- Subjects must have documented diagnosis of multiple myeloma and have measurable disease
- All subjects must have had at least 2 prior lines of anti-myeloma therapy. Induction therapy followed by stem cell transplant and consolidation/maintenance will be considered as one line
All subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last anti-myeloma therapy.
- Primary refractory: Subjects who have never achieved any response better than progressive disease (PD) to any previous line of anti-myeloma therapy.
- Relapsed and refractory: Subjects who have relapsed after having achieved at least stable disease (SD) to at least one prior regimen and then developed progressive disease (PD) on or within 60 days of completing their last anti-myeloma therapy.
- Subjects must have also undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen).
- All subjects must have received adequate prior alkylator therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
Exclusion Criteria:
- Pregnant or breastfeeding females
- Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
- ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy
- Patients unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study
Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 1,000/µL
- Platelet count < 75,000/µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
- Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula
- Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
- Serum glutamic oxaloacetic transaminase (SGOT) /aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT) /alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
- Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or ≥ 3.0 x upper limit of normal (ULN) for subjects with hereditary benign hyperbilirubinaemia
- Peripheral neuropathy ≥ Grade 2
Patients who received any of the following within the last 14 days of initiation of study treatment:
- Plasmapheresis
- Major surgery (kyphoplasty is not considered major surgery)
- Radiation therapy
- Use of any anti-myeloma drug therapy
Sites / Locations
- Nagoya City University Hospital
- Tokai University Hospital
- Saitama Medical Center, Saitama Medical University
- National Cancer Center Hospital
- Kyusyu University Hospital
- Kameda General Hospital
- Niigata Cancer Center Hospital
- Okayama Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
pomalidomide
Arm Description
Patients will receive pomalidomide orally on Days 1-21 of each 28-day cycle until when/if a discontinuation criterion, e.g., disease progression, development of an unacceptable toxicity, voluntary withdrawal, or pomalidomide is in market for the target indication.
Outcomes
Primary Outcome Measures
Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events
Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events
Secondary Outcome Measures
Maximum observed plasma concentration (Cmax)
Maximum observed plasma concentration (Cmax)
Time to maximum observed plasma concentration (tmax)
Time to maximum observed plasma concentration (tmax)
Area under the plasma concentration-time curve (AUC0-t)
Area under the plasma concentration-time curve (AUC0-t)
Apparent total plasma clearance (CL/F)
Apparent total plasma clearance (CL/F)
Apparent total volume of distribution (Vz/F)
Apparent total volume of distribution (Vz/F)
Estimate of the terminal elimination half-life in plasma (t1/2)
Estimate of the terminal elimination half-life in plasma (t1/2)
Safety (the number of participants with adverse events, incidence, severity, causality)
Safety (the number of participants with adverse events, incidence, severity, causality)
Progression-free survival
Progression-free survival
Myeloma response
Myeloma response
Time to Response
Time to Response
Duration of Response
Duration of Response
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01568294
Brief Title
Japanese Phase 1 Study to Evaluate Tolerated Dose, Safety, and Efficacy of Pomalidomide in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Official Title
A Phase 1, Multicenter, Open-label, Dose-escalation Study in Japan to Determine the Tolerated Dose and to Evaluate the Safety, Efficacy, and Pharmacokinetics of Pomalidomide Alone or in Combination With Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
April 1, 2012 (Actual)
Primary Completion Date
July 8, 2015 (Actual)
Study Completion Date
July 8, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the tolerated dose of pomalidomide and also to evaluate the pharmacokinetics, safety and efficacy of pomalidomide in patients with refractory or relapsed and refractory multiple myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
pomalidomide
Arm Type
Experimental
Arm Description
Patients will receive pomalidomide orally on Days 1-21 of each 28-day cycle until when/if a discontinuation criterion, e.g., disease progression, development of an unacceptable toxicity, voluntary withdrawal, or pomalidomide is in market for the target indication.
Intervention Type
Drug
Intervention Name(s)
pomalidomide
Intervention Description
2 mg or 4mg oral pomalidomide once per day on Days 1-21 of a 28-day cycle
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events
Description
Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events
Time Frame
Up to 28 Days
Secondary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax)
Description
Maximum observed plasma concentration (Cmax)
Time Frame
Up to 28 days
Title
Time to maximum observed plasma concentration (tmax)
Description
Time to maximum observed plasma concentration (tmax)
Time Frame
Up 28 days
Title
Area under the plasma concentration-time curve (AUC0-t)
Description
Area under the plasma concentration-time curve (AUC0-t)
Time Frame
Up to 28 days
Title
Apparent total plasma clearance (CL/F)
Description
Apparent total plasma clearance (CL/F)
Time Frame
Up to 28 days
Title
Apparent total volume of distribution (Vz/F)
Description
Apparent total volume of distribution (Vz/F)
Time Frame
Up to 28 days
Title
Estimate of the terminal elimination half-life in plasma (t1/2)
Description
Estimate of the terminal elimination half-life in plasma (t1/2)
Time Frame
Up to 28 days
Title
Safety (the number of participants with adverse events, incidence, severity, causality)
Description
Safety (the number of participants with adverse events, incidence, severity, causality)
Time Frame
Up to 2 years
Title
Progression-free survival
Description
Progression-free survival
Time Frame
Up to 28 days
Title
Myeloma response
Description
Myeloma response
Time Frame
Up to 28 days
Title
Time to Response
Description
Time to Response
Time Frame
Up to 28 days
Title
Duration of Response
Description
Duration of Response
Time Frame
Up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must be ≥ 20 years of age at the time of signing the informed consent document
The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
Must be able to adhere to the study visit schedule and other protocol requirements
Subjects must have documented diagnosis of multiple myeloma and have measurable disease
All subjects must have had at least 2 prior lines of anti-myeloma therapy. Induction therapy followed by stem cell transplant and consolidation/maintenance will be considered as one line
All subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last anti-myeloma therapy.
Primary refractory: Subjects who have never achieved any response better than progressive disease (PD) to any previous line of anti-myeloma therapy.
Relapsed and refractory: Subjects who have relapsed after having achieved at least stable disease (SD) to at least one prior regimen and then developed progressive disease (PD) on or within 60 days of completing their last anti-myeloma therapy.
Subjects must have also undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen).
All subjects must have received adequate prior alkylator therapy.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
Exclusion Criteria:
Pregnant or breastfeeding females
Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
≥ Grade 3 rash during prior thalidomide or lenalidomide therapy
Patients unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study
Any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) < 1,000/µL
Platelet count < 75,000/µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula
Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
Serum glutamic oxaloacetic transaminase (SGOT) /aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT) /alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or ≥ 3.0 x upper limit of normal (ULN) for subjects with hereditary benign hyperbilirubinaemia
Peripheral neuropathy ≥ Grade 2
Patients who received any of the following within the last 14 days of initiation of study treatment:
Plasmapheresis
Major surgery (kyphoplasty is not considered major surgery)
Radiation therapy
Use of any anti-myeloma drug therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Toru Sasaki
Organizational Affiliation
Celgene K.K
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya City University Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Tokai University Hospital
City
Isehara
State/Province
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Saitama Medical Center, Saitama Medical University
City
Kawagoe
State/Province
Saitama
ZIP/Postal Code
350-8550
Country
Japan
Facility Name
National Cancer Center Hospital
City
Tyuuou
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Kyusyu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Kameda General Hospital
City
Kamogawa
ZIP/Postal Code
296-1602
Country
Japan
Facility Name
Niigata Cancer Center Hospital
City
Niigata
ZIP/Postal Code
951-8566
Country
Japan
Facility Name
Okayama Medical Center
City
Okayama
ZIP/Postal Code
701-1192
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
26292221
Citation
Matsue K, Iwasaki H, Chou T, Tobinai K, Sunami K, Ogawa Y, Kurihara M, Midorikawa S, Zaki M, Doerr T, Iida S. Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Cancer Sci. 2015 Nov;106(11):1561-7. doi: 10.1111/cas.12772. Epub 2015 Nov 4.
Results Reference
background
PubMed Identifier
30792190
Citation
Mark TM, Forsberg PA, Rossi AC, Pearse RN, Pekle KA, Perry A, Boyer A, Tegnestam L, Jayabalan D, Coleman M, Niesvizky R. Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma. Blood Adv. 2019 Feb 26;3(4):603-611. doi: 10.1182/bloodadvances.2018028027.
Results Reference
background
Learn more about this trial
Japanese Phase 1 Study to Evaluate Tolerated Dose, Safety, and Efficacy of Pomalidomide in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
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