A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study (NIMBUS)

Celgene

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: pomalidomide; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01311687

2010-019820-30 (EudraCT Number)

CC-4047-MM-003

Details and patient eligibility

About

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.

Enrollment: 455 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must be ≥ 18 years of age
• Subjects must have documented diagnosis of multiple myeloma and have measurable disease
• Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
• Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
• All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
• All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [≥ partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
• Patients must have received adequate prior alkylator therapy
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation
• Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
• Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study
• Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study

Exclusion criteria

• Any of the following laboratory abnormalities:

  • Absolute neutrophil count (ANC) < 1,000/μL
  • Platelet count < 75,000/ μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells
  • Creatinine clearance < 45 mL/min
  • Corrected serum calcium > 14 mg/dL
  • Hemoglobin ≤ 8 g/dL
  • Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
  • Serum total bilirubin > 2.0 mg/dL

• Previous therapy with pomalidomide

• Hypersensitivity to thalidomide, lenalidomide, or dexamethasone

• Resistance to high-dose dexamethasone used in the last line of therapy

• Peripheral neuropathy ≥ Grade 2

• Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant

• Subjects who are planning for or who are eligible for stem cell transplant

• Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris

• Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy

• Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment

• Subjects with conditions requiring chronic steroid or immunosuppressive treatment

• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

• Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide

• Subjects unable or unwilling to undergo antithrombotic prophylactic treatment

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form

• Pregnant or breastfeeding females

• Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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455 participants in 2 patient groups

Pomalidomide + Low-Dose Dexamethasone

Experimental group

Description:

Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.

Treatment:

Drug: pomalidomide

Drug: Dexamethasone

High-Dose Dexamethasone

Active Comparator group

Description:

Participants received 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.

Treatment:

Drug: Dexamethasone