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Adult Myelodysplastic SyndromePhase 2NCT01772420

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

A Phase 2 study testing Eltrombopag Olamine, Laboratory Biomarker Analysis and Lenalidomide in people with Adult Myelodysplastic Syndrome and Anemia, run by Albert Einstein College of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Eltrombopag Olamine, Laboratory Biomarker Analysis and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesUnited States
Study dates
Oct 2012to 9 Jul 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES (not Outcome Measures):

  1. 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):

  1. 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.

  1. 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

Being tested
Eltrombopag Olamine, Laboratory Biomarker Analysis, Lenalidomide
Medical subject headings
Anemia, Refractory, with Excess of Blasts, Anemia, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Eltrombopag OlamineDrug

    Also called Promacta, SB-497115-GR

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

Study groups in NCT01772420
Study groupRoleWhat they receive
Arm A (lenalidomide, eltrombopag olamine)ExperimentalPatients 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.
Receives: Drug: Eltrombopag Olamine; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide
Arm B (eltrombopag olamine, lenalidomide)ExperimentalPatients 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.
Receives: Drug: Eltrombopag Olamine; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Demonstrating Overall Hematologic Improvement (HI)

    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.

    Measured: 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 outcomes (6)

  1. Number of Patients With Hematologic Improvement in Platelet Counts (HI-P)

    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.

    Measured: 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

  2. Number of Patients With Hematologic Improvement in Erythrocyte Counts (HI-E)

    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.

    Measured: 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

  3. Number of Patients With Hematologic Improvement in Neutrophil Counts (HI-N)

    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.

    Measured: 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

  4. Time to Attain Hematologic Improvement (HI)

    Time to hematologic improvement as determined by median time required to achieve HI response.

    Measured: 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

  5. Duration of Hematologic Improvement (HI)

    Duration to hematologic improvement as determined by median duration of HI response.

    Measured: Time to progression/relapse following hematologic improvement, at completion of final cycle and treatment discontinuation; up to 6 years

  6. Number of Patients With Clinically Significant Bleeding Events

    Number of Patients With Clinically Significant Bleeding Events

    Measured: Treatment initiation through study completion, up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2013 (estimated)
  2. Study startOct 2012
  3. Primary completion9 Jul 2020
  4. Study completion9 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01772420
Sponsor's protocol ID
2012-407
Other IDs
NCI-2013-01219, P30CA013330, 115479, RV--MDS-PI-0645
Status last verified
Jul 2023
First submitted
15 Jan 2013
Last updated
27 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Eltrombopag Olamine, Laboratory Biomarker Analysis and Lenalidomide in people with Adult Myelodysplastic Syndrome and Anemia, run by Albert Einstein College of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01772420.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

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