Study of Pomalidomide to Evaluate the Pharmacokinetics and Safety for Patients With Multiple Myeloma and Impaired Renal Function (POM Renal) (POM Renal)

A Phase 1 Multi-Center, Open-Label, Dose-Escalation Study to Determine the Pharmacokinetics and Safety of Pomalidomide When Given in Combination With Low Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Impaired Renal Function

The purpose of this study is to determine the pharmacokinetics (PK) and safety for the combination of pomalidomide (POM) + low-dose dexamethasone (LD- DEX) in subjects with relapsed or refractory Multiple Myeloma (RRMM) and impaired renal function.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Renal Impairment
• Intervention / Treatment: Drug: 4 mg Oral POM + 40 mg Oral DEX; Drug: 2 mg Oral POM + 40 mg Oral DEX

Detailed Description

The primary objective of the study is to determine the PK and safety for the combination of POM + (LD-DEX) in subjects with RRMM and impaired renal function.

The secondary objective of the study is to evaluate the efficacy of POM + (LD_DEX) in subjects with RRMM and impaired renal function.

This is a 3+3 dose escalation design, with one cohort each for patients with severely impaired renal function patients (CrCl < 30 mL/min) requiring and not requiring dialysis respectively. There will also be one control cohort with normal renal function, these patients will receive 4 mg POM. Dosing will be 21 days out of a 28 day cycle.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • L'Hotel Dieu de Quebec
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Research Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Must be ≥ 18 years at the time of signing the informed consent form
2. Must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures
3. Must be able to adhere to the study visit schedule and other protocol requirements
4. Must have documented diagnosis of relapsed or refractory multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours)
5. Must have had at least 1 prior anti-myeloma regimen
6. Must have documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
8. Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe
9. Females must agree to abstain from breastfeeding during study participation and for 28 following discontinuation from study treatment
10. 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 study treatment, even if he has undergone a successful vasectomy
11. Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from study treatment
12. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from study treatment
13. All subjects must agree not to share medication

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Peripheral neuropathy ≥ Grade 2
2. Non-secretory multiple myeloma

3. Any of the following laboratory abnormalities:

   • Absolute neutrophil count (ANC) < 1,000/µL
   • Platelet count < 75,000/µL
   • Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
   • Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
   • Serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) or serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) > 3.0 x upper limit of normal (ULN)
   • Serum total bilirubin > 2.0 mg/dL

4. Prior history of malignancies, other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years from initiating study treatment, with the following exceptions:

   • Basal cell carcinoma of the skin
   • Squamous cell carcinoma of the skin
   • Carcinoma in situ of the cervix
   • Carcinoma in situ of the breast
   • Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system).
5. Previous therapy with Pomalidomide
6. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
7. Rash ≥ Grade 3 during prior thalidomide or lenalidomide therapy
8. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide

9. Subjects with any one of the following:

   • Congestive heart failure (New York Heart Association Class III or IV)
   • Myocardial infarction within 12 months prior to starting study treatment
   • Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris

10. Subjects who received any of the following within the last 14 days of initiation of study treatment:

    • Plasmapheresis
    • Major surgery (kyphoplasty is not considered major surgery)
    • Radiation therapy (with the exception of radiation therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is refractory to narcotic analgesics)
    • Any anti-myeloma drug therapy
11. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
12. Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to initiating study treatment
13. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study
14. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
15. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
16. Pregnant or breastfeeding females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4 mg Oral POM + 40 mg Oral DEX; Oral POM at 4 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle	Drug: 4 mg Oral POM + 40 mg Oral DEX; Other Names: Dexamethasone; Pomalidomide (POM)
EXPERIMENTAL: 2 mg Oral POM + 40 mg Oral DEX; Oral POM at 2 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle	Drug: 2 mg Oral POM + 40 mg Oral DEX; Other Names: Dexamethasone; Pomalidomide (POM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK-Area under the plasma concentration time curve (AUC)	PK-Area under the plasma concentration time curve (AUC)	Up to 24 times over 7 months
PK-Time to maximum plasma concentration (Cmax)	PK-Time to maximum plasma concentration (Cmax)	24 times over 7 months
PK-Apparent total body clearance (CL/F)	PK-Apparent total body clearance (CL/F)	24 times up to 7 months
PK-Renal clearance (CLr)	PK-Renal clearance (CLr)	24 times over 7 months
PK-Apparent volume of distribution (V/F)	PK-Apparent volume of distribution (V/F)	24 times over 7 months
PK-Effective terminal half-life (T1/2)	PK-Effective terminal half-life (T1/2)	24 times over 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Number of participants with adverse events (AEs)	Up to 5 years
Number of participants alive	Number of participants alive	Up to 5 years
Time to response	Time to response	Up to 5 years
Duration of response	Duration of response	Up to 5 years

Collaborators and Investigators

• Sponsor: Celgene

Publications and helpful links

General Publications

• Li Y, Wang X, O'Mara E, Dimopoulos MA, Sonneveld P, Weisel KC, Matous J, Siegel DS, Shah JJ, Kueenburg E, Sternas L, Cavanaugh C, Zaki M, Palmisano M, Zhou S. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function. Clin Pharmacol. 2017 Nov 8;9:133-145. doi: 10.2147/CPAA.S144606. eCollection 2017.
• Kavanaugh A, Gladman DD, Edwards CJ, Schett G, Guerette B, Delev N, Teng L, Paris M, Mease PJ. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019 May 10;21(1):118. doi: 10.1186/s13075-019-1901-3.
• Matous J, et al. MM-008 trial: Pharmacokinetics (PK) and tolerability of pomalidomide plus low-dose dexamethasone (POM plus LoDEX) in relapsed/refractory multiple myeloma (RRMM) patients with renal impairment (RI). Presented at: American Society of Clinical Oncology ASCO 2013, May 31-June 4, 2013, Chicago, IL. Abstract No. 8585. JClinOncol 2013;31(suppl 15):8585-8585.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2012
• Primary Completion (ACTUAL): August 7, 2018
• Study Completion (ACTUAL): August 7, 2018

Study Registration Dates

• First Submitted: April 10, 2012
• First Submitted That Met QC Criteria: April 11, 2012
• First Posted (ESTIMATE): April 12, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Pomalidomide; dialysis; renal impairment; hemodialysis; MM; RRMM; dexamethasone; Pomalyst; severe renal impairment; POM; Pomalidomide for multiple myeloma; multiple myeloma patients with renal impairment; Pomalidomide for patients with renal impairment due to multiple myeloma; impaired renal function in multiple myeloma; CrCl ≤ 30 mL/min; Creatinine less than 30; clinical trial in subjects with multiple myeloma with renal impairement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Kidney Diseases; Urologic Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Thalidomide; Pomalidomide
• Other Study ID Numbers: CC-4047-MM-008