Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

NCT01497093 | Completed Phase 1

• 1 other identifier: CC-4047-MM-005
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) of pomalidomide in combination with bortezomib and low-dose dexamethasone in subjects with relapsed or refractory multiple myeloma

Conditions

Multiple Myeloma

Keywords

Myeloma; Multiple Myeloma; Relapsed Multiple Myeloma; Relapsed and Refractory Multiple Myeloma; Refractory Myeloma; Resistant Multiple Myeloma; Treatment-resistant Multiple Myeloma; Pomalidomide; Lenalidomide-resistant

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To determine the maximum tolerated dose (MTD)

  Up to 2 years

Secondary Outcomes (5)

• Adverse events

  Up to 7 years

• Overall Survival

  Up to 7 years

• Response Rate

  Up to 7 years

• Duration of response

  Up to 7 years

• Time to response

  Up to 7 years

Study Arms (1)

Pomalidomide/Bortezomib/Dexamethasone

EXPERIMENTAL

1, 2, 3 or 4 mg of pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1 or 1.3 mg/m2 of bortezomib administered intravenously or subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and dexamethasone 20 mg/day \[≤ 75 years old\] or 10 mg/day \[\> 75 years old\] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression

Drug: Pomalidomide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Pomalidomide DRUG

Pomalidomide 1, 2, 3, or 4 mg will be taken orally on Days 1-14 of a 21-day cycle

Also known as: CC-4047, Oral Pomalidomide

Pomalidomide/Bortezomib/Dexamethasone

Bortezomib DRUG

Bortezomib 1 or 1.3 mg/m2 will be administered intravenously or subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression

Also known as: Velcade

Pomalidomide/Bortezomib/Dexamethasone

Dexamethasone DRUG

Dexamethasone 20 mg/day \[≤ 75 years old\] or 10 mg/day \[\> 75 years old\] will be taken orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression

Pomalidomide/Bortezomib/Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Must be ≥ 18 years at the time of signing the informed consent form.
• 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).
• Subjects must have had at least 1 but no greater than 4 prior anti-myeloma therapies.
• Subjects must have received at least 2 consecutive cycles of prior treatment with lenalidomide and must be refractory to their last lenalidomide-containing regimen (either as a single agent or in combination).
• Subjects must have received at least 2 consecutive cycles of prior treatment with a proteasome inhibitor-containing regimen, but must not be refractory to bortezomib (either as a single agent or in combination).
• Subjects must have documented progression during or after their last anti-myeloma therapy.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

You may not qualify if:

• Subjects who are refractory to bortezomib either as single agent or in combination.
• Subjects with peripheral neuropathy ≥ Grade 2
• Subjects with non-secretory multiple myeloma
• Subjects with any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 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
• 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 Transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) \> 3.0 x upper limit of normal (ULN)
• Serum total bilirubin \> 1.5 x ULN
• Subjects with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years. Except the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (T1a or T1b using the TNM \[tumor, nodes, metastasis\] clinical staging system) or prostate cancer that is curative.
• Subjects with previous therapy with Pomalidomide
• Subjects with hypersensitivity to thalidomide, lenalidomide, bortezomib, boron, mannitol, or dexamethasone
• Subjects with ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy

Sponsors & Collaborators

• Celgene: lead
• Multiple Myeloma Research Consortium: collaborator

Study Sites (6)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115-6084, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (3)

• Richardson PG, Hofmeister CC, Raje NS, Siegel DS, Lonial S, Laubach J, Efebera YA, Vesole DH, Nooka AK, Rosenblatt J, Doss D, Zaki MH, Bensmaine A, Herring J, Li Y, Watkins L, Chen MS, Anderson KC. Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma. Leukemia. 2017 Dec;31(12):2695-2701. doi: 10.1038/leu.2017.173. Epub 2017 Jun 2.

  PMID: 28642620 BACKGROUND

• Pelligra CG, Parikh K, Guo S, Chandler C, Mouro J, Abouzaid S, Ailawadhi S. Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed-refractory Multiple Myeloma in the United States. Clin Ther. 2017 Oct;39(10):1986-2005.e5. doi: 10.1016/j.clinthera.2017.08.010. Epub 2017 Sep 28.

  PMID: 28967482 BACKGROUND

• Moreau P, Dimopoulos MA, Richardson PG, Siegel DS, Cavo M, Corradini P, Weisel K, Delforge M, O'Gorman P, Song K, Chen C, Bahlis N, Oriol A, Hansson M, Kaiser M, Anttila P, Raymakers R, Joao C, Cook G, Sternas L, Biyukov T, Slaughter A, Hong K, Herring J, Yu X, Zaki M, San-Miguel J. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Eur J Haematol. 2017 Sep;99(3):199-206. doi: 10.1111/ejh.12903. Epub 2017 Jun 14.

  PMID: 28504846 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

pomalidomide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Amine Bensmaine, MD

  Celgene

  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: December 20, 2011
• First Posted: December 22, 2011
• Study Start: February 15, 2012
• Primary Completion: July 23, 2019
• Study Completion: July 23, 2019
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

US (6)