Phase 2
N=12
A Pharmacokinetic And Pharmacodynamic Study Of Oral Lenalidomide (Revlimid) In Subjects With Low- Or Intermediate-1-Risk Myelodysplastic Syndromes
Low- or Intermediate-1-risk Myelodysplastic Syndrome (MDS)
Bottom Line
View on ClinicalTrials.gov: NCT00910858 ↗Enrolled (actual)
12
Serious AEs
38.5%
Results posted
Sep 2013
Primary outcome: Primary: PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide — 817 ng*h/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lenalidomide (Drug); Recombinant human erythropoietin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Celgene Corporation
- Primary completion
- Apr 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide |
817 | — |
| PRIMARY Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide |
563; 315; 248 | — |
| SECONDARY PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) |
179; 101; 78.3 | — |
| SECONDARY Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) |
185; 104; 80.7 | — |
| SECONDARY PK Phase: Terminal Half-life (t1/2) |
3.72; 4.14; 3.58 | — |
| SECONDARY PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose |
65.1; 67.9; 62.2 | — |
| SECONDARY Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose |
34.0; 35.4; 32.5 | — |
| SECONDARY Time to Grade 4 Neutropenia or Thrombocytopenia |
69.0; 28.0; 53.0; 29.0 | — |
| SECONDARY Percentage of Participants With a Erythroid Response Across All Phases |
17.6; 40.0; 85.7; 5.9; 0; 0 | — |
| SECONDARY Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level |
62.5; 47.8; 53.8; 37.5; 39.1; 38.5 | — |
| SECONDARY Change From Baseline in Bone Marrow Cellularity and Correlation With Grade 4 Myelosuppression |
— | — |
| SECONDARY Marrow-infiltrating Lymphocyte (MIL) Number and Cytolytic Activity |
— | — |
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).
Eligibility Criteria
Inclusion Criteria
- 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 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.
- Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥3 years.
- Any serious medical condition or psychiatric illness that will prevent the patient from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
- Known human immunodeficiency virus (HIV-1) positivity.
Data sourced from ClinicalTrials.gov (NCT00910858). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.