Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia

July 24, 2023 updated by: Albert Einstein College of Medicine

Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia in Low or Intermediate I Myelodysplastic Syndrome (MDS)

This phase II trial studies how well lenalidomide (LEN) and eltrombopag olamine (ELT) work in treating patients with symptomatic anemia in low or intermediate myelodysplastic syndrome (MDS). Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Eltrombopag olamine may increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving lenalidomide and eltrombopag olamine may be an effective treatment for myelodysplastic syndrome.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES (not Outcome Measures):

I. To evaluate the rate of hematologic improvement of the eltrombopag (eltrombopag olamine)/lenalidomide combination (as per Modified International Working Group [IWG] criteria).

II. To evaluate the safety and tolerability of the combination.

SECONDARY OBJECTIVES (not Outcome Measures):

I. To compare the time to hematologic improvement. II. To evaluate the duration of hematologic improvement III. To evaluate the effect of combination treatment on platelet counts, platelet transfusions and bleeding events.

IV. To evaluate the frequency of bone marrow response (complete response [CR] + partial response [PR]) and cytogenetic response.

V. To evaluate the relationship between mutations in bone marrow stem cells and response.

VI. To evaluate the relationship between various stem and progenitor alterations and response.

OUTLINE: Patients are initially assigned to 1 of 2 treatment arms.

ARM A: Patients with platelet counts >= 50,000 receive lenalidomide orally (PO) daily or every other day (QOD) on days 1-21. If platelet counts fall below 50,000, patients discontinue lenalidomide and receive eltrombopag olamine PO daily or QOD until platelet count is maintained above 50,000 for 2 weeks. Patients then resume lenalidomide PO daily or QOD. If platelets fall below 50,000 again, patients receive eltrombopag olamine as before. When platelet counts are maintained above 50,000 for 2 weeks, patients resume lenalidomide concurrently with eltrombopag for all subsequent courses.

ARM B: Patients with platelet counts < 50,000 receive eltrombopag olamine PO daily or QOD on days 1-28 until platelet counts is maintained above 50,000 for 2 weeks. Patients then receive treatment as in Arm A.

In both arms, treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Eligible patients with a diagnosis of MDS or non-proliferative chronic myelomonocytic leukemia (CMML) (WBC ≤ 12,000/mL) of at least 3-month duration according to WHO criteria and International Prognostic Scoring System categories of low or intermediate-1-risk disease. Patients either had symptomatic anemia untransfused with hemoglobin ≤ 10 g/dL in the 8 weeks before starting the study or had RBC transfusion dependence (i.e., ≥ 2 units/mo) confirmed 8 weeks before starting the study and/or PLTs <50,000 k/uL with hemoglobin >10.0 g/dL. Patients must not have received prior therapy with LEN (for > 2 months) nor ELT

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient must have a documented diagnosis of myelodysplastic syndrome (MDS) of at least three months duration (MDS duration >= 3 months) according to World Health Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cells [WBC] =< 12,000/L)
  • Patients must have International Prognostic Scoring System (IPSS) categories of low- or intermediate-1-risk disease
  • Patients must have symptomatic anemia untransfused with hemoglobin =< 9.5 g/dL within 8 weeks of registration or with red blood cell (RBC) transfusion-dependence (i.e., >= 2 units/month) confirmed for a minimum of 8 weeks before randomization
  • Patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients with cytogenetic failure and =< 10% marrow blasts will be eligible
  • Patients must be off all disease modifying therapy for MDS for 28 days prior to initiation of study treatment; patients may receive hydrocortisone prophylactically to prevent transfusion reactions
  • Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be >= 20% or a serum ferritin >= 100 ng/100 mL or soluble transferring receptor < 5 mg/L.
  • Women must not be pregnant or breastfeeding; females of childbearing potential should have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL); the first test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing lenalidomide
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program; able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)
  • Women of childbearing potential and sexually active males must agree to use 2 methods of an accepted and effective method of contraception and counseled on the potential teratogenic effects of lenalidomide; effective contraception must be used by patients for at least 4 weeks before beginning lenalidomide therapy, during lenalidomide therapy, during dose interruptions and for 4 weeks following discontinuation of lenalidomide therapy; reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months; two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method; females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed; sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be females of childbearing potential; it is not known whether CC-5013 (lenalidomide) is present in the semen of patients receiving the drug; therefore, males receiving CC-5013 (lenalidomide) must always use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
  • Patients must not have received prior therapy with lenalidomide (for more than 2 months) nor eltrombopag
  • Patients must not have uncontrolled hypertension
  • Patients must have absolute neutrophil count (ANC) >= 500 cells/L (0.5 x 10^9/L)
  • Eastern Cooperative Oncology Group (ECOG) performance 0-3
  • Subject is able to understand and comply with protocol requirements and instructions
  • Patient has signed and dated informed consent
  • Prothrombin time (PT/international normalized ratio [INR]) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range at baseline

Exclusion Criteria:

  • Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a corrected QT interval (QTc) > 450 msec
  • Patients determined to be at increased risk of arterial or venous thrombosis by the investigator
  • Bone marrow fibrosis that leads to a dry tap
  • Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test) at screening or pre-dose on day 1
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication
  • Patients with documented liver cirrhosis
  • Patients with splenomegaly with a spleen size > 16 cm

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A (lenalidomide, eltrombopag olamine)

Patients with baseline platelet counts >= 50,000 receive lenalidomide PO daily or QOD on days 1-21. If platelet counts fall below 50,000, patients discontinue lenalidomide and receive eltrombopag olamine PO daily or QOD until platelet count is maintained above 50,000 for 2 weeks. Patients then resume lenalidomide PO daily or QOD. If platelets fall below 50,000 again, patients receive eltrombopag olamine as before. When platelet counts are maintained above 50,000 for 2 weeks, patients resume lenalidomide concurrently with eltrombopag for all subsequent courses.

Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • Revlimid
  • CC5013
  • CDC 501
Drug: Eltrombopag Olamine
Given PO
Other Names:
  • Promacta
  • SB-497115-GR
Experimental: Arm B (eltrombopag olamine, lenalidomide)

Patients with baseline platelet counts < 50,000 receive eltrombopag olamine PO daily or QOD on days 1-28 until platelet count is maintained above 50,000 for 2 weeks. Patients then receive treatment as in Arm A.

Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • Revlimid
  • CC5013
  • CDC 501
Drug: Eltrombopag Olamine
Given PO
Other Names:
  • Promacta
  • SB-497115-GR

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Patients Demonstrating Overall Hematologic Improvement (HI)
Time Frame: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
The number of patients demonstrating overall Hematologic Improvement (HI) was assessed based on the MDS 2006 IWG criteria. The IWG criteria for HI define specific responses of cytopenia in the 3 hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N) as demonstrated in corresponding outcome measures. Responses must have sustained for at minimum of 8 weeks for the participant to be included in the tally.
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Patients With Hematologic Improvement in Platelet Counts (HI-P)
Time Frame: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
The Number of Patients with Hematologic Improvement in Platelet Counts (HI-P) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an absolute increase of ≥ 30 × 10^9/L (for those patients starting with > 20 × 10^9/L platelets) or an increase from < 20 × 10^9/L to > 20 × 10^9/L along with an increase of at least 100%, were deemed to have demonstrated HI-P improvement.
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Number of Patients With Hematologic Improvement in Erythrocyte Counts (HI-E)
Time Frame: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
The Number of Patients with Hematologic Improvement in Erythrocyte Counts (HI-E) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an Hgb increase by ≥ 1.5 g/dL were deemed to have improvement in HI-E. Only transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response.
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Number of Patients With Hematologic Improvement in Neutrophil Counts (HI-N)
Time Frame: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
The Number of Patients with Hematologic Improvement in Neutrophil Counts (HI-N) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an increase of at least 100% and an absolute increase > 0.5 × 10^9/L were determined to have shown an improvement in HI-N.
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Time to Attain Hematologic Improvement (HI)
Time Frame: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Time to hematologic improvement as determined by median time required to achieve HI response.
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Duration of Hematologic Improvement (HI)
Time Frame: Time to progression/relapse following hematologic improvement, at completion of final cycle and treatment discontinuation; up to 6 years
Duration to hematologic improvement as determined by median duration of HI response.
Time to progression/relapse following hematologic improvement, at completion of final cycle and treatment discontinuation; up to 6 years
Number of Patients With Clinically Significant Bleeding Events
Time Frame: Treatment initiation through study completion, up to 2 years
Number of Patients With Clinically Significant Bleeding Events
Treatment initiation through study completion, up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Albert Einstein College of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Amit K Verma, Albert Einstein College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 9, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 9, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 21, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 27, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012-407 (Albert Einstein College of Medicine)
  • P30CA013330 (U.S. NIH Grant/Contract)
  • NCI-2013-01219 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RV--MDS-PI-0645 (Other Identifier: Celgene Tracking Number)
  • 115479 (Other Identifier: GlaxoSmithKline Tracking Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Anemia

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings