Japanese Phase 2 Study to Evaluate the Efficacy and Safety of Pomalidomide in Subjects With Relapsed and Refractory Multiple Myeloma

NCT02011113 | Completed Phase 2 Results

• 1 other identifier: CC-4047-MM-011
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pomalidomide in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Pomalidomide,; CC-4047,; Dexamethasone,; Relapsed and refractory multiple myeloma,; phase 2

Outcome Measures

Primary Outcomes (2)

• Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria

  Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

  From the first dose until the data cut-off date of 03 Sept 2014; Maximum time in follow-up was 36.0 weeks.

• Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria (Later Cut-off Date)

  Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

  From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Secondary Outcomes (9)

• Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria

  From first dose until the data cut-off date of 03 September 2014; maximum time in follow-up was 36.0 weeks

• Time to Response

  From the first dose until the data cut-off date of 03 September 2014. Maximum time on follow-up was 36.0 weeks.

• Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria (Later Cut-off Date)

  From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

• Time to Response (Later Cut-off Date)

  From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

• Kaplan-Meier Estimates of Duration of Response

  From first dose until the data cut-off date of 03 September 2014; maximum time for follow-up was 36 weeks

Study Arms (1)

Pomalidomide plus dexamethasone

EXPERIMENTAL

Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Pomalidomide DRUG

4 mg oral pomalidomide once daily Days 1-21 of each 28-day cycle

Also known as: CC-4047

Pomalidomide plus dexamethasone

Dexamethasone DRUG

40 mg or 20 mg oral dexamethasone once daily on Days 1, 8, 15, 22 of each 28-day cycle

Also known as: LenaDex

Pomalidomide plus dexamethasone

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 before any study related assessments/procedures are conducted.
• \. Must be able to adhere to the study visit schedule and other protocol requirements.
• \. Have a documented diagnosis of multiple myeloma and have relapsed and refractory disease. Subjects must have received at least 2 prior therapies. Subjects must have relapsed after having achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed progressive disease(PD). Subjects must also have documented evidence of progressive disease(PD) during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry (refractory disease).
• \. Subjects must have 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).
• \. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
• \. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Must agree to comply to pomalidomide Pregnancy Prevention Risk Management Plan.

You may not qualify if:

• \. Pregnant or breastfeeding females 2. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone 3. ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy 4. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study 5. Any of the following laboratory abnormalities:
• Absolute neutrophil count \< 1,000/µL
• Platelet count \< 75,000/µL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 30,000/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells
• Creatinine Clearance \< 45 mL/min according to Cockcroft-Gault formula
• Cockcroft-Gault estimation of Creatinine Clearance:
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L)
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior Red blood cell transfusion or recombinant human erythropoietin use is permitted)
• Serum glutamic oxaloacetic transaminase(SGOT)/aspartate aminitransferase(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 hyperbilirubinemia.
• \. Subjects with any one of the following:
• Congestive heart failure (New York Heart Association Class III or IV)
• Myocardial infarction within 12 months prior to starting study treatment
• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris 7. Peripheral neuropathy ≥ Grade 2. 8. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
• Basal or Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (14)

Celgene Trial Site

Nagoya, Aichi-ken, 467-8602, Japan

Location

Celgene Trial Site

Kamogawa, Chiba, 298-8602, Japan

Location

Celgene Trial Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Celgene Trial Site

Hiroshima, Hiroshima, 734-8551, Japan

Location

Celgene Trial Site

Mito, Ibaragi, 311-3193, Japan

Location

Celgene Trial Site

Isehara, Kanagawa, 259-1193, Japan

Location

Celgene Trial Site

Kyoto, Kyoto, 602-8566, Japan

Location

Celgene Trial Site

Niigata, Niigata, 951-8566, Japan

Location

Celgene Trial Site

Okayama, Okayama-ken, 701-1192, Japan

Location

Celgene Trial Site

Osaka, Osaka, 543-8555, Japan

Location

Celgene Trial Site

Tokyo, Tokyo, 104-0045, Japan

Location

Celgene Trial Site

Tokyo, Tokyo, 150-8935, Japan

Location

Celgene Trial Site

Tokyo, Tokyo, 160-8582, Japan

Location

Celgene Trial Site

Tokyo, Tokyo, 162-8655, Japan

Location

Related Publications (1)

• Ichinohe T, Kuroda Y, Okamoto S, Matsue K, Iida S, Sunami K, Komeno T, Suzuki K, Ando K, Taniwaki M, Tobinai K, Chou T, Kaneko H, Iwasaki H, Uemura C, Tamakoshi H, Zaki MH, Doerr T, Hagiwara S. A multicenter phase 2 study of pomalidomide plus dexamethasone in patients with relapsed and refractory multiple myeloma: the Japanese MM-011 trial. Exp Hematol Oncol. 2016 Apr 18;5:11. doi: 10.1186/s40164-016-0040-7. eCollection 2015.

  PMID: 27096106 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

pomalidomide; Dexamethasone

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Anne McClain, Senior Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Toru Sasaki, Director

  Celgene K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 13, 2013
• Study Start: December 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2015
• Last Updated: November 1, 2016
• Results First Posted: November 10, 2015

Record last verified: 2016-09

Locations

JP (14)