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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Oncotherapeutics
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Oncotherapeutics
ClinicalTrials.gov Identifier:
NCT01541332
First received: February 20, 2012
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: Pomalidomide
Drug: Pegylated Liposomal Doxorubicin (PLD)
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Oncotherapeutics:

Primary Outcome Measures:
  • MTD of Pomalidomide [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin

  • Overall Response Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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:
  • Number of Patients with Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Phase 2: To establish the number of patients with adverse events when using the combination of pomalidomide, dexamethasone and pegylated liposomal doxorubicin

  • Time to Progression [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Phase 2: Defined as the time from initiation of therapy to progressive disease

  • Progression-free Survival [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Phase 2: Defined as the time from initiation of therapy to progressive disease or death from any cause, which ever occurs first

  • Time to First Response [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Phase 2: Defined as the time from the initiation of therapy to the first evidence of a confirmed response (CR, VGPR, PR or MR)

  • Duration of Response [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Phase 2: Defined as the time from first response to progressive disease

  • Overall Survival [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Phase 2: Defined as the time from initiation of therapy to death from any cause or last follow-up visit


Estimated Enrollment: 68
Study Start Date: February 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  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: NCT01541332

Contacts
Contact: Carley E Turner 310-623-1206 cturner@oncotherapeutics.com
Contact: Liv Thulin 310-623-1200 lthulin@oncotherapeutics.com

Locations
United States, California
Roy and Patricia Disney Family Cancer Center Recruiting
Burbank, California, United States, 91505
Contact: Donna Fernando    818-748-4723    donna.fernando@providence.org   
Contact: Nikko Grub    818-748-4723    nikko.grub@providence.org   
Principal Investigator: Martina Zalom, MD         
California Cancer Associates for Research and Excellence Recruiting
Encinitas, California, United States, 92024
Contact: Beth Kimball, RN    760-452-3909    bkimball@pacificoncology.com   
Contact: Jacqui Noble    760-452-3909    jnoble@pacificoncology.com   
Principal Investigator: Alberto Bessudo, MD         
Hematology Oncology Medical Group Recruiting
Fresno, California, United States, 93720
Contact: Debbie Cosgrove    559-447-4949    hemonc7130@yahoo.com   
Contact: Shelley Sonksen    559-447-4930    ssonke@pacbell.net   
Principal Investigator: Thomas Hackett, MD         
Pacific Cancer Care Recruiting
Salinas, California, United States, 93901
Contact: Monica Castillo, RN    831-755-1701 ext 124    mocastillo@pacificcancercare.com   
Contact: Anne Haghighat, RN    831-755-1701 ext 167    ahaghighat@pacificcancercare.com   
Principal Investigator: Laura Stampleman, MD         
Cancer Center of Santa Barbara Recruiting
Santa Barbara, California, United States, 93105
Contact: Heidi Heitkamp    805-898-2117    hheitkamp@ccsb.org   
Contact: Megan Wingo    805-898-2779    mwingo@ccsb.org   
Principal Investigator: Thomas Woliver, MD         
Mission Hope Cancer Center Recruiting
Santa Maria, California, United States, 93454
Contact: Carol Herrin, RN    805-346-3463    carol.herrin@dignityhealth.org   
Principal Investigator: Kathleen Kennedy, MD         
James R Berenson, MD, Inc. Recruiting
West Hollywood, California, United States, 90069
Contact: James Berenson, MD    310-623-1222    jberenson@imbcr.org   
Contact: Regina Swift, RN, BSN    310-623-1222    rswift@berensononcology.com   
Sub-Investigator: Youram Nassir, MD         
Sub-Investigator: Shahrooz Eshaghian, MD         
Principal Investigator: James Berenson, MD         
United States, Illinois
Illinois Cancer Specialists Recruiting
Niles, Illinois, United States, 60714
Contact: Pian Moy, RN    847-827-9060    pian.moy@usoncology.com   
Contact: Lisbeth Lynn    847-827-9060    lisbeth.lynn@usoncology.com   
Principal Investigator: Leonard Klein, MD         
Sponsors and Collaborators
Oncotherapeutics
Celgene Corporation
Investigators
Principal Investigator: James R Berenson, MD Oncotherapeutics
  More Information

No publications provided

Responsible Party: Oncotherapeutics
ClinicalTrials.gov Identifier: NCT01541332     History of Changes
Other Study ID Numbers: PO-MM-PI-0049, PDD-2011
Study First Received: February 20, 2012
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Oncotherapeutics:
relapsed refractory
multiple myeloma
pomalidomide
Doxil
dexamethasone
Oncotherapeutics

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
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Liposomal doxorubicin
Pomalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 25, 2014