A Pharmacokinetic And Pharmacodynamic Study Of Oral Lenalidomide (Revlimid) In Subjects With Low- Or Intermediate-1-Risk Myelodysplastic Syndromes

NCT00910858 | Completed Phase 1 Results DMC

• 1 other identifier: CC-5013-PK-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess pharmacokinetic and pharmacodynamic characteristics of oral lenalidomide monotherapy administered to patients with Low- or Intermediate-1-risk Myelodysplastic Syndrome (MDS).

Conditions

Low- or Intermediate-1-risk Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (2)

• PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide

  Area under the plasma concentration-time curve from Time 0 to 24 hours post-dose for lenalidomide after a single dose, calculated using the log-linear trapezoidal method.

  On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.

• Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide

  Area under the plasma concentration-time curve from Time 0 to 5 hours postdose for lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days, calculated using the log-linear trapezoidal method.

  On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.

Secondary Outcomes (10)

• PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)

  On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.

• Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)

  On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.

• PK Phase: Terminal Half-life (t1/2)

  On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.

• PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose

  On Day -7 at predose and over the intervals of 0-5, 5-8, 8-12, and 12-24 hours postdose.

• Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose

  On Day 14, at predose and over the interval of 0-5 hours postdose.

Study Arms (2)

10 mg Lenalidomide

EXPERIMENTAL

Participants in the Pharmacokinetic Phase received a single 10 mg oral dose of lenalidomide on Day -7. During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure. During the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Drug: Lenalidomide; Drug: Recombinant human erythropoietin

15 mg Lenalidomide Non-del 5q

EXPERIMENTAL

Following the enrollment of the first 25 patients into the Monotherapy Phase, a second group of 15 patients with low- or intermediate-1-risk MDS not associated with a del 5q (non-del 5q) cytogenetic abnormality were enrolled to receive 15 mg of lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure. During the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 15 mg lenalidomide in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Drug: Lenalidomide; Drug: Recombinant human erythropoietin

Interventions

Lenalidomide DRUG

Lenalidomide 5-mg capsules for oral administration

Also known as: Revlimid

10 mg Lenalidomide; 15 mg Lenalidomide Non-del 5q

Recombinant human erythropoietin DRUG

Recombinant human erythropoietin (rhu-EPO) subcutaneous injection of 40,000 units.

10 mg Lenalidomide; 15 mg Lenalidomide Non-del 5q

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must understand and voluntarily sign an informed consent form.
• Age ≥18 years at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Documented diagnosis of MDS that meets International Prognostic Scoring System (IPSS) criteria for Low- to Intermediate-1-risk disease.
• Must have a diagnosis of low- or intermediate- risk MDS without a del 5q chromosomal abnormality (patients taking 15 mg starting dose only).
• Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure.
• Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥4 transfusions of RBCs within 56 days of randomization or symptomatic anemia (hemoglobin \< 9.0 g/dl).
• Failed prior treatment with recombinant human erythropoietin (rhu-EPO) (≥ 30,000 U/week x 6) or serum erythropoietin (EPO) concentration ≥500 mU/ml (hemoglobin \< 9.0 g/dl).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device \[IUD\], hormonal \[birth control pills, injections, or implants\], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods, if needed.

You may not qualify if:

• Pregnant or lactating females.
• Prior therapy with lenalidomide.
• Proliferative white blood cell (WBC) ≥12,000/µL) chronic myelomonocytic leukemia (CMML).
• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
• Any of the following lab abnormalities:
• Absolute neutrophil count (ANC) \<500 cells/µL (0.5 x 10\^9/L)
• Platelet count \<50,000/µL (50 x 10\^9/L)
• Serum creatinine \> upper limit of normal (ULN)
• Serum glutamic oxaloacetic transaminase/aspartate transaminase (SGOT/AST) or serum glutamic pyruvic transaminase/alanine transaminase (SGPT/ALT) \>2.0 x ULN
• Serum total bilirubin \>2.0 mg/dL (34 µmol/L)
• Prior ≥grade-2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction to thalidomide.
• Prior desquamating (blistering) rash while taking thalidomide.
• Patients with ≥grade-2 neuropathy.
• Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
• Use of cytotoxic chemotherapeutic agents, erythropoietin, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the first day of study drug treatment.

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Komrokji RS, Lancet JE, Swern AS, Chen N, Paleveda J, Lush R, Saba HI, List AF. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood. 2012 Oct 25;120(17):3419-24. doi: 10.1182/blood-2012-03-415661. Epub 2012 Aug 30.

  PMID: 22936658 RESULT

MeSH Terms

Interventions

Lenalidomide

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Robert Knight, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: June 1, 2009
• Study Start: January 1, 2005
• Primary Completion: April 1, 2006
• Study Completion: May 1, 2009
• Last Updated: September 30, 2013
• Results First Posted: September 30, 2013

Record last verified: 2013-07

Locations

US (1)