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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00833833
First received: January 30, 2009
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
Drug: Pomalidomide
Drug: Dexamethasone
Drug: Aspirin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Multi-center, Randomized, Open-label Dose Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of CC-4047 Alone Or in Combination With Low-dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma Who Have Received Prior Treatment That Includes Lenalidomide and Bortezomib

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Phase 1: Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 [ Time Frame: Up to Day 28 (Cycle 1) ] [ Designated as safety issue: Yes ]

    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

  • Phase 2: Kaplan-Meier Estimates of Progression-free Survival (PFS) as of the 01 April 2011 Cut-off [ Time Frame: up to 67 weeks ] [ Designated as safety issue: No ]

    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.


  • Phase 2: Percentage of Participants With Progression-Free Survival (PFS) Events as of the 01 April 2011 Cut-off [ Time Frame: up to 67 weeks ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Single-Agent Pomalidomide as of the 01 April 2011 Cut-off [ Time Frame: Up to week 104 ] [ Designated as safety issue: Yes ]

    Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

    Data collection is ongoing and future data results will be included as available.


  • 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 [ Time Frame: Up to week 126 ] [ Designated as safety issue: Yes ]

    TEAEs that occurred during Phase 1 after dexamethasone was added to pomalidomide treatment.

    Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

    Data collection is ongoing and future data results will be included as available.


  • Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as of the 01 April 2011 Cut-off [ Time Frame: Up to week 70 ] [ Designated as safety issue: Yes ]

    Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

    Data collection is ongoing and future data results will be included as available.


  • 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 [ Time Frame: up to 70 weeks ] [ Designated as safety issue: No ]

    IRAC used EBMT criteria to assess myeloma response:

    • Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of lytic bone lesions, plus other factors)
    • Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others
    • Minimal Response (MR)- 25-49% reduction in serum monoclonal paraprotein plus others
    • Stable Disease (SD)- not MR or progressive disease (PD)
    • Progressive Disease (PD)- reappearance of monoclonal paraprotein, lytic bone lesions, other
    • Not Evaluable (NE).

    Data collection is ongoing and future data results will be included as available.


  • Phase 2: Kaplan-Meier Estimates of Duration of Response as of the 01 April 2011 Cut-off [ Time Frame: up to 70 weeks ] [ Designated as safety issue: No ]

    Duration of myeloma response is defined as the time from when the response criteria are first met for partial response (PR) or better, until the first date the response criteria are met for progressive disease (PD) or until the participant dies from any cause, whichever occurs first. Duration of response for participants last known to be alive with no progression after a complete response (CR) or PR was censored at the date of last adequate response assessment. Participants with confirmed responses that occur after receiving any other anti-myeloma therapy (except for adding dexamethasone to the pomalidomide treatment arm), including radiation therapy initiated after baseline, was censored at the last adequate assessment prior to the initiation of such treatment.

    Response was assessed by the Independent Response Adjudication Committee (IRAC) using European Group for Blood and Bone Marrow Transplant (EBMT) criteria as described in the previous outcome.


  • Phase 2: Time to Response as of the 01 April 2011 Cut-off [ Time Frame: up to 70 weeks ] [ Designated as safety issue: No ]

    Time to myeloma response is defined as the time from randomization to the time the response criteria for complete response (CR) or partial response (PR) are first met.

    Response was assessed by the Independent Response Adjudication Committee (IRAC) using European Group for Blood and Bone Marrow Transplant (EBMT) criteria as described previously.

    Data collection is ongoing and future data results will be included as available.


  • Phase 2: Kaplan-Meier Estimates of Overall Survival as of the 01 April 2011 Cut-off [ Time Frame: up to 70 weeks ] [ Designated as safety issue: No ]

    Overall survival was defined as the time between randomization and death. Participants who die, regardless of the cause of the death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the subject was known to be alive, or clinical cut-off date if it was earlier.

    Data collection is ongoing and future data results will be included as available.



Enrollment: 259
Study Start Date: June 2008
Estimated Study Completion Date: September 2015
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1: 2 mg pomalidomide
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin
Experimental: Phase 1: 3 mg pomalidomide
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin
Experimental: Phase 1: 4 mg pomalidomide
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin
Experimental: Phase 1: 5 mg pomalidomide
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin
Experimental: Phase 2: pomalidomide + dexamethasone
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin
Experimental: Phase 2: pomalidomide
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
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Other Names:
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
oral dexamethasone
Other Name: dexamethasone sodium phosphate
Drug: Aspirin
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.
Other Name: aspirin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Peripheral neuropathy ≥ Grade 2
  • Use of any anti-myeloma drug therapy within 14 days of the initiation of study drug treatment or use of any experimental non-drug therapy within 28 days of the initiation of study drug treatment
  • Radiation therapy within 14 days of initiation of study drug treatment Inability or unwillingness to comply with birth control requirements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00833833

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, Colorado
Colorado Blood Cancer Institute HCA-HealthONE/Rocky Mountain Blood and Marrow Transplant Program
Denver, Colorado, United States, 80218
United States, Florida
H. Lee Moffitt Cancer and Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48105
United States, Minnesota
Mayo Clinic Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University - Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, New Jersey
The Cancer Center Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Mt. Sinai Hospital
New York, New York, United States, 10029
United States, Ohio
The Ohio State University - James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Canada, Alberta
Cross Cancer Center
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Vancover General Hospital - Diamond Health Care
Vancouver, British Columbia, Canada, V5Z 1M9
University of Calgary - Tom Baker Cancer Center
Vancouver, British Columbia, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Hospital - UHN
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Royal Victoria Hospital - McGill University
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Christian J Jacques, MD Celgene Corporation
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00833833     History of Changes
Other Study ID Numbers: CC-4047-MM-002
Study First Received: January 30, 2009
Results First Received: March 8, 2013
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Aspirin
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Thalidomide
Analgesics
Analgesics, Non-Narcotic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antiemetics

ClinicalTrials.gov processed this record on October 22, 2014