Clinical trial NCT01568294: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-04-02
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events
timeFrame: Up to 28 Days
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to 28 days
measure: Time to maximum observed plasma concentration (tmax)
timeFrame: Up 28 days
measure: Area under the plasma concentration-time curve (AUC0-t)
timeFrame: Up to 28 days
measure: Apparent total plasma clearance (CL/F)
timeFrame: Up to 28 days
measure: Apparent total volume of distribution (Vz/F)
timeFrame: Up to 28 days
measure: Estimate of the terminal elimination half-life in plasma (t1/2)
timeFrame: Up to 28 days
measure: Safety (the number of participants with adverse events, incidence, severity, causality)
timeFrame: Up to 2 years
measure: Progression-free survival
timeFrame: Up to 28 days
measure: Myeloma response
timeFrame: Up to 28 days
measure: Time to Response
timeFrame: Up to 28 days
measure: Duration of Response
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kawagoe
country: Japan
facility: Saitama Medical Center, Saitama Medical University
state: Saitama
city: Tyuuou
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyusyu University Hospital
city: Kamogawa
country: Japan
facility: Kameda General Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama Medical Center
Study officials:
affiliation: Celgene K.K
name: Toru Sasaki
role: STUDY_DIRECTOR
References:
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.
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.