Japanese Phase 1 Study to Evaluate Tolerated Dose, Safety, and Efficacy of Pomalidomide in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01568294
• Other study ID #: CC-4047-MM-004
• Status: Completed
• Phase: Phase 1
• Start date: April 1, 2012
• Est. completion date: July 8, 2015

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 8, 2015
• Est. primary completion date: July 8, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• pomalidomide
2 mg or 4mg oral pomalidomide once per day on Days 1-21 of a 28-day cycle

Locations

Country	Name	City	State
Japan	Kyusyu University Hospital	Fukuoka
Japan	Tokai University Hospital	Isehara	Kanagawa
Japan	Kameda General Hospital	Kamogawa
Japan	Saitama Medical Center, Saitama Medical University	Kawagoe	Saitama
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama Medical Center	Okayama
Japan	National Cancer Center Hospital	Tyuuou	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 28 Days
Secondary	Maximum observed plasma concentration (Cmax)	Maximum observed plasma concentration (Cmax)	Up to 28 days
Secondary	Time to maximum observed plasma concentration (tmax)	Time to maximum observed plasma concentration (tmax)	Up 28 days
Secondary	Area under the plasma concentration-time curve (AUC0-t)	Area under the plasma concentration-time curve (AUC0-t)	Up to 28 days
Secondary	Apparent total plasma clearance (CL/F)	Apparent total plasma clearance (CL/F)	Up to 28 days
Secondary	Apparent total volume of distribution (Vz/F)	Apparent total volume of distribution (Vz/F)	Up to 28 days
Secondary	Estimate of the terminal elimination half-life in plasma (t1/2)	Estimate of the terminal elimination half-life in plasma (t1/2)	Up to 28 days
Secondary	Safety (the number of participants with adverse events, incidence, severity, causality)	Safety (the number of participants with adverse events, incidence, severity, causality)	Up to 2 years
Secondary	Progression-free survival	Progression-free survival	Up to 28 days
Secondary	Myeloma response	Myeloma response	Up to 28 days
Secondary	Time to Response	Time to Response	Up to 28 days
Secondary	Duration of Response	Duration of Response	Up to 28 days