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

Phase 1

Completed

• Conditions: Multiple Myeloma; Renal Impairment
• Interventions: Drug: 2 mg Oral POM + 40 mg Oral DEX; Drug: 4 mg Oral POM + 40 mg Oral DEX

• Registration Number: NCT01575925
• Lead Sponsor: Celgene

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-04-10
• Study First Submitted QC: 2012-04-11
• Study First Posted: 2012-04-12
• Study Start: 2012-06-01
• Primary Completion: 2018-08-07
• Study Completion: 2018-08-07
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-03
• Last Update Posted: 2022-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
2 mg Oral POM + 40 mg Oral DEX	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
4 mg Oral POM + 40 mg Oral DEX	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Duration of response	Up to 5 years	Duration of response
Number of participants alive	Up to 5 years	Number of participants alive
Number of participants with adverse events (AEs)	Up to 5 years	Number of participants with adverse events (AEs)
Time to response	Up to 5 years	Time to response

Trial Locations

Locations (9)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Ingalls Cancer Research Center; 🇺🇸 Harvey, Illinois, United States

L'Hotel Dieu de Quebec; 🇨🇦 Quebec, Canada

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Queen Elizabeth II Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada