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

NCT01568294 | Completed Phase 1

• 1 other identifier: CC-4047-MM-004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 8

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Maximum observed plasma concentration (Cmax)

  Up to 28 days

• Time to maximum observed plasma concentration (tmax)

  Up 28 days

• Area under the plasma concentration-time curve (AUC0-t)

  Up to 28 days

• Apparent total plasma clearance (CL/F)

  Up to 28 days

• Apparent total volume of distribution (Vz/F)

  Up to 28 days

Study Arms (1)

pomalidomide

EXPERIMENTAL

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.

Drug: pomalidomide

Interventions

pomalidomide DRUG

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

pomalidomide

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (8)

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Tokai University Hospital

Isehara, Kanagawa, 259-1193, Japan

Location

Saitama Medical Center, Saitama Medical University

Kawagoe, Saitama, 350-8550, Japan

Location

National Cancer Center Hospital

Tyuuou, Tokyo, 104-0045, Japan

Location

Kyusyu University Hospital

Fukuoka, 812-8582, Japan

Location

Kameda General Hospital

Kamogawa, 296-1602, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Okayama Medical Center

Okayama, 701-1192, Japan

Location

Related Publications (2)

• 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.

  PMID: 26292221 BACKGROUND

• 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.

  PMID: 30792190 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Toru Sasaki

  Celgene K.K

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 2, 2012
• Study Start: April 1, 2012
• Primary Completion: July 8, 2015
• Study Completion: July 8, 2015
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

JP (8)