MTD, Safety, and Efficacy of Pomalidomide (CC-4047) Alone or With Low-dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma

NCT00833833 | Completed Phase 1 Results DMC

• 1 other identifier: CC-4047-MM-002
• Study Type: interventional
• Target: 259
• Locations: 2 countries
• Sites: 19

Brief Summary

The purpose of this study is to determine the maximum tolerated dose and effectiveness of the study drug (CC-4047) Alone Or in Combination With Low-dose Dexamethasone as treatment for patients with relapsed and refractory multiple myeloma

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Phase 1: Participants With Dose-Limiting Toxicities (DLT) in Cycle 1

  The maximum tolerated dose was defined as the highest dose level at which no more than 1 of 6 participants experiences a DLT within the first 28-day cycle. DLTs were defined as: * Grade 4 neutropenia or thrombocytopenia * Febrile neutropenia * Grade 3 or 4 nausea, vomiting or diarrhea despite optimal symptomatic treatment * Serum transaminase \> 20 \* upper limit of normal (ULN) * Serum transaminase \> 5 \* ULN for \>= 7 days * Delay of the start of cycle 2 by \>7 days due to pomalidomide-related adverse event

  Up to Day 28 (Cycle 1)

• Phase 2: Kaplan-Meier Estimates of Progression-free Survival (PFS) as of the 01 April 2011 Cut-off

  Progression free survival (PFS) is the time from randomization to the first documentation of disease progression or death from any cause during study, whichever occurs earlier. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC). For the primary PFS analysis, participants who withdrew for any reason or received another antimyeloma therapy (except adding dexamethasone to the Phase 2: Pomalidomide arm) without documented PD (as determined by the IRAC review) were censored on the date of their last adequate response assessment, prior to receiving any other anti-myeloma therapy. Subjects who were still active at the time of the data cut-off date without PD (as determined by the IRAC) were censored on the date of their last adequate response assessment. Data collection is ongoing and future data results will be included as available.

  up to 67 weeks

• Phase 2: Percentage of Participants With Progression-Free Survival (PFS) Events as of the 01 April 2011 Cut-off

  Percentage of participants with the progression-free survival events: disease progression and death. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC). Data collection is ongoing and future data results will be included as available.

  up to 67 weeks

Secondary Outcomes (7)

• Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Single-Agent Pomalidomide as of the 01 April 2011 Cut-off

  Up to week 104

• Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Pomalidomide and Dexamethasone as of the 01 April 2011 Cut-off

  Up to week 126

• Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as of the 01 April 2011 Cut-off

  Up to week 70

• Phase 2: Summary of Best Myeloma Response As Assessed by Independent Response Adjudication Committee (IRAC) Using European Group for Blood and Bone Marrow Transplant (EBMT) Criteria as of the 01 April 2011 Cut-off

  up to 70 weeks

• Phase 2: Kaplan-Meier Estimates of Duration of Response as of the 01 April 2011 Cut-off

  up to 70 weeks

Study Arms (6)

Phase 1: 2 mg pomalidomide

EXPERIMENTAL

Pomalidomide 2 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Phase 1: 3 mg pomalidomide

EXPERIMENTAL

Pomalidomide 3 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Phase 1: 4 mg pomalidomide

EXPERIMENTAL

Pomalidomide 4 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Phase 1: 5 mg pomalidomide

EXPERIMENTAL

Pomalidomide 5 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Phase 2: pomalidomide + dexamethasone

EXPERIMENTAL

Combination therapy of 4 mg pomalidomide given once per day on Days 1-21 of each 28-day cycle and the starting dose of dexamethasone (determined by age) on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose of dexamethasone was 40 mg for participants who were ≤ 75 years of age and 20 mg for participants who were \> 75 years of age. Dose reduction steps for dexamethasone were provided for drug-related toxicities.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Phase 2: pomalidomide

EXPERIMENTAL

4 mg pomalidomide was given once per day on Days 1-21 of each 28-day cycle until PD. Participants in the single agent pomalidomide treatment arm who developed confirmed PD at any time had the option to receive oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle at the starting dose of 20 or 40 mg depending on age in addition to their current dose of pomalidomide, or to discontinue treatment.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: Aspirin

Interventions

Pomalidomide DRUG

1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply

Also known as: CC-4047, Pomalyst

Phase 1: 2 mg pomalidomide; Phase 1: 3 mg pomalidomide; Phase 1: 4 mg pomalidomide; Phase 1: 5 mg pomalidomide; Phase 2: pomalidomide; Phase 2: pomalidomide + dexamethasone

Dexamethasone DRUG

oral dexamethasone

Also known as: dexamethasone sodium phosphate

Phase 1: 2 mg pomalidomide; Phase 1: 3 mg pomalidomide; Phase 1: 4 mg pomalidomide; Phase 1: 5 mg pomalidomide; Phase 2: pomalidomide; Phase 2: pomalidomide + dexamethasone

Aspirin DRUG

As prophylactic anti-thrombotic treatment, all participants were given aspirin 81-100 mg daily (commercial supply) unless contraindicated. If aspirin was contraindicated, participants were given another form of anti-thrombotic therapy according to hospital guidelines or physician preference.

Phase 1: 2 mg pomalidomide; Phase 1: 3 mg pomalidomide; Phase 1: 4 mg pomalidomide; Phase 1: 5 mg pomalidomide; Phase 2: pomalidomide; Phase 2: pomalidomide + 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 greater than or equal to 18 years at the time of signing the informed consent form
• 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. Patients must have received at least 2 prior therapies. Patients 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 PD. Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
• Patients 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)
• Measurable levels of myeloma paraprotein in serum (greater than or equal to 0.5 g/dL) or urine (greater than or equal 0.2 g/dL excreted in a 24 hour collection sample)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Females of childbearing potential (FCBP) \[An FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months)\] must agree to refrain from becoming pregnant for 28 days prior to initiation of study drug, while on study drug and for 28 days after discontinuation of study drug and must agree to regular pregnancy testing during this timeframe.
• All patients must also agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study
• Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study even if he has undergone a successful vasectomy. Males must also agree to refrain from donating blood, semen or sperm during the above referenced timeframe.
• All patients must agree not to share medication with another person.

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.
• Any serious concurrent medical conditions that may make the patient non-evaluable or put the patient's safety at risk.
• Pregnant or lactating females
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000 cells/mm3
• Platelet count \< 75,000/mm3 for patients in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 30,000/mm3 for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
• Serum creatinine \> 3.0 mg/dL
• Serum glutamic oxaloacetic transaminase/Aspartate transaminase (SGOT/AST) or Serum Glutamic Pyruvate Transaminase/Alanine transaminase (SGPT/ALT) \> 3.0 X upper limit of normal (ULN)
• Serum total bilirubin \> 2.0 mg/dL
• Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection
• Hypersensitivity to thalidomide, lenalidomide, or dexamethasone

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (19)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer CenterDivision of Hematology/Oncology

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic - Arizona

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute Department of Medicine

Buffalo, New York, 14263, United States

Location

Mt. Sinai Hospital

New York, New York, 10029, United States

Location

Ohio State University Arthur G. James Cancer Hospital

Columbus, Ohio, 43210-1240, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 2T9, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret Hospital and University of Toronto

Toronto, Ontario, M5G 2M9, Canada

Location

Royal Victoria Hosptial

Montreal, Quebec, H3A 1A1, Canada

Location

Related Publications (3)

• Siegel DS, Weisel KC, Dimopoulos MA, Baz R, Richardson P, Delforge M, Song KW, San Miguel JF, Moreau P, Goldschmidt H, Cavo M, Jagannath S, Yu X, Hong K, Sternas L, Zaki M, Palumbo A. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016 Dec;57(12):2833-2838. doi: 10.1080/10428194.2016.1177181. Epub 2016 Jun 7.

  PMID: 27267105 DERIVED

• Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson KC. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. doi: 10.1182/blood-2013-11-538835. Epub 2014 Jan 13.

  PMID: 24421329 DERIVED

• Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, Sullivan D, Alsina M, Schlossman R, Ghobrial IM, Doss D, Loughney N, McBride L, Bilotti E, Anand P, Nardelli L, Wear S, Larkins G, Chen M, Zaki MH, Jacques C, Anderson KC. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood. 2013 Mar 14;121(11):1961-7. doi: 10.1182/blood-2012-08-450742. Epub 2012 Dec 14.

  PMID: 23243282 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; Dexamethasone; dexamethasone 21-phosphate; Aspirin

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Lars A Sternas, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 30, 2009
• First Posted: February 2, 2009
• Study Start: June 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: September 1, 2015
• Last Updated: April 27, 2016
• Results First Posted: April 25, 2013

Record last verified: 2016-03

Locations

US (14); CA (5)