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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT01575925

Collaborator

(none)

Enrollment

Locations

Arms

74.2

Actual Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Renal Impairment	Drug: 4 mg Oral POM + 40 mg Oral DEX Drug: 2 mg Oral POM + 40 mg Oral DEX	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Aug 7, 2018

Actual Study Completion Date :

Aug 7, 2018

Arms and Interventions

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: Pomalidomide (POM) Dexamethasone
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: Pomalidomide (POM) Dexamethasone

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:

Pomalidomide (POM)

Dexamethasone

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:

Pomalidomide (POM)

Dexamethasone

Outcome Measures

Primary Outcome Measures

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-Time to maximum plasma concentration (Cmax) [24 times over 7 months]
PK-Time to maximum plasma concentration (Cmax)
PK-Apparent total body clearance (CL/F) [24 times up to 7 months]
PK-Apparent total body clearance (CL/F)
PK-Renal clearance (CLr) [24 times over 7 months]
PK-Renal clearance (CLr)
PK-Apparent volume of distribution (V/F) [24 times over 7 months]
PK-Apparent volume of distribution (V/F)
PK-Effective terminal half-life (T1/2) [24 times over 7 months]
PK-Effective terminal half-life (T1/2)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Must be ≥ 18 years at the time of signing the informed consent form
Must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures
Must be able to adhere to the study visit schedule and other protocol requirements
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)
Must have had at least 1 prior anti-myeloma regimen
Must have documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
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
Females must agree to abstain from breastfeeding during study participation and for 28 following discontinuation from study treatment
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
Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from study treatment
All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from study treatment
All subjects must agree not to share medication

Exclusion Criteria:

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

Peripheral neuropathy ≥ Grade 2
Non-secretory multiple myeloma
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

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).

Previous therapy with Pomalidomide
Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
Rash ≥ Grade 3 during prior thalidomide or lenalidomide therapy
Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
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

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

Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
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
Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
Pregnant or breastfeeding females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	Ingalls Cancer Research Center	Harvey	Illinois	United States	60426
4	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
5	Weill Cornell Medical College	New York	New York	United States	10065
6	Cleveland Clinic	Cleveland	Ohio	United States	44195
7	MD Anderson Cancer Center	Houston	Texas	United States	77030
8	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
9	L'Hotel Dieu de Quebec	Quebec		Canada	G1R 2J6