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Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01541332
Recruitment Status : Unknown
Verified March 2016 by Oncotherapeutics.
Recruitment status was:  Active, not recruiting
First Posted : February 29, 2012
Last Update Posted : March 10, 2016
Celgene Corporation
Information provided by (Responsible Party):

Brief Summary:
The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to past treatment) multiple myeloma. Different dosages (amount of study drug) of pomalidomide are first being tested to determine if there are any side effects or risks associated with combining this study drug with the other two listed. Once the optimal dose is decided on, the study will change its focus to determining the effectiveness of the study drug in this combination.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Pomalidomide Drug: Pegylated Liposomal Doxorubicin (PLD) Drug: Dexamethasone Phase 1 Phase 2

Detailed Description:

This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment, and a follow-up period.

Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression.

Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below.

Cohort 1 Pomalidomide* - 2 mg, Dexamethasone** - 40 mg, PLD** - 5 mg/m2

Cohort 2 Pomalidomide* - 3 mg, Dexamethasone** - 40 mg, PLD** - 5 mg/m2

Cohort 3 Pomalidomide* - 4 mg, Dexamethasone** - 40 mg, PLD** - 5 mg/m2

* PO Days 1-21

** IV Days 1, 4, 8 and 11

In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma
Study Start Date : February 2012
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Pomalidomide + PLD + Dexamethasone
Pomalidomide + Pegylated Liposomal Doxorubicin + Dexamethasone in an open label, dose escalation study
Drug: Pomalidomide
Pomalidomide administered to 3 cohorts of subjects at escalating doses of 2 (cohort 1), 3 (cohort 2) and 4 mg/dose (cohort 3) per orem (PO). Doses are to be administered once-a-day, for the first 21 days, as part of a 28-day treatment cycle, followed by a 7-day rest period.
Other Name: CC-4047

Drug: Pegylated Liposomal Doxorubicin (PLD)

Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.

PLD will be given at a dose of 5.0 mg/m2 as a 60 minute IV infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle.

Other Name: Doxil

Drug: Dexamethasone
Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.
Other Name: Decadron

Primary Outcome Measures :
  1. MTD of Pomalidomide [ Time Frame: 12 months ]
    Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin

  2. Overall Response Rate [ Time Frame: 24 months ]
    Phase 2: To determine efficacy as evidenced by the best overall response rate (CR + VGPR + PR + MR) following treatment with pomalidomide, dexamethasone and pegylated liposomal doxorubicin

Secondary Outcome Measures :
  1. Number of Patients with Adverse Events [ Time Frame: 24 months ]
    Phase 2: To establish the number of patients with adverse events when using the combination of pomalidomide, dexamethasone and pegylated liposomal doxorubicin

  2. Time to Progression [ Time Frame: 24 Months ]
    Phase 2: Defined as the time from initiation of therapy to progressive disease

  3. Progression-free Survival [ Time Frame: 24 Months ]
    Phase 2: Defined as the time from initiation of therapy to progressive disease or death from any cause, which ever occurs first

  4. Time to First Response [ Time Frame: 24 Months ]
    Phase 2: Defined as the time from the initiation of therapy to the first evidence of a confirmed response (CR, VGPR, PR or MR)

  5. Duration of Response [ Time Frame: 24 Months ]
    Phase 2: Defined as the time from first response to progressive disease

  6. Overall Survival [ Time Frame: 24 Months ]
    Phase 2: Defined as the time from initiation of therapy to death from any cause or last follow-up visit

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of MM based on standard criteria (Durie 1986)
  • Currently has MM with measurable disease, defined as:

    • a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or
    • urine monoclonal protein levels of at least 200 mg/24 hours
    • for patients without measurable serum and urine M-protein levels, an abnormal free light chain ratio (normal value: 0.26 - 1.65)
  • Currently has progressive MM that has relapsed or is refractory, defined as:

    • For the phase 1: Relapsed following stabilization or a response to at least one anti-myeloma regimen or refractory defined as progressed while receiving an anti-myeloma treatment
    • For the phase 2: Refractory to lenalidomide as demonstrated by progressive disease while on lenalidomide or that relapsed within 8 weeks of the last dose of lenalidomide either as a single agent or in combination.
    • Prior treatment with four days or less of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for MM will not be considered a regimen
  • Able to adhere to the study visit schedule and other protocol requirements
  • ECOG performance status of 2 or greater at study entry
  • Life-expectancy of greater than 3 months
  • Lab tests within study ranges at study entry:

    • Absolute neutrophil count > 1.5 x 109/L
    • Platelet count > 75 x 109/L
    • Hemoglobin > 8 g/dL
    • Calculated or measured creatinine clearance > 30 mL/minute
    • Total bilirubin < 1.5 x upper limit of normal (ULN)
    • AST (SGOT) and ALT (SGPT) < 2 x ULN
    • Serum potassium within the normal range
  • Females of childbearing potential must have a negative serum or urine pregnancy test.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to ASA may use warfarin or low molecular weight heparin)

Exclusion Criteria:

  • POEMS syndrome
  • Plasma cell leukemia
  • Primary amyloidosis
  • Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  • Impaired cardiac function or clinically significant cardiac diseases
  • Severe hypercalcemia
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (Kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a subject with a recent history of kyphoplasty with the medical monitor)
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
  • Received the following prior therapy:

    • Pomalidomide
    • Chemotherapy within 3 weeks of study drugs (6 wks for nitrosoureas)
    • Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of study drugs
    • Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before study drugs
    • Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
    • Use of any other experimental drug or therapy within 28 days of study drugs
  • Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide, lenalidomide or doxorubicin.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Concurrent use of other anti-cancer agents or treatments
  • Known positivity for human immunodeficiency virus (HIV) or hepatitis B or C; baseline testing for HIV and hepatitis B or C is not required

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01541332

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United States, California
Roy and Patricia Disney Family Cancer Center
Burbank, California, United States, 91505
California Cancer Associates for Research and Excellence
Encinitas, California, United States, 92024
Hematology Oncology Medical Group
Fresno, California, United States, 93720
Pacific Cancer Care
Salinas, California, United States, 93901
Cancer Center of Santa Barbara
Santa Barbara, California, United States, 93105
Mission Hope Cancer Center
Santa Maria, California, United States, 93454
James R Berenson, MD, Inc.
West Hollywood, California, United States, 90069
United States, Illinois
Illinois Cancer Specialists
Niles, Illinois, United States, 60714
Sponsors and Collaborators
Celgene Corporation
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Principal Investigator: James R Berenson, MD Oncotherapeutics
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Responsible Party: Oncotherapeutics Identifier: NCT01541332    
Other Study ID Numbers: PO-MM-PI-0049
PDD-2011 ( Other Identifier: Oncotherapeutics )
First Posted: February 29, 2012    Key Record Dates
Last Update Posted: March 10, 2016
Last Verified: March 2016
Keywords provided by Oncotherapeutics:
relapsed refractory
multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Liposomal doxorubicin
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic