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A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma

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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of Pomalidomide

Outcome Description:

Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

James R Berenson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

February 2012

Completion Date:

April 2014

Related Keywords:

  • Multiple Myeloma
  • relapsed refractory
  • multiple myeloma
  • pomalidomide
  • Doxil
  • dexamethasone
  • Oncotherapeutics
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



James R Berenson, MD, Inc. West Hollywood, California  90069