Lenalidomide and Eltrombopag Olamine in Treating Patients With Symptomatic Anemia in Low or Intermediate Myelodysplastic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Amit Verma, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01772420
First received: January 15, 2013
Last updated: March 2, 2015
Last verified: March 2015
  Purpose

This phase II trial studies how well lenalidomide and eltrombopag olamine works in treating patients with symptomatic anemia in low or intermediate myelodysplastic syndrome. 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.


Condition Intervention Phase
Adult Myelodysplastic Syndrome
Anemia
Chronic Myelomonocytic Leukemia
Drug: Lenalidomide
Drug: Eltrombopag Olamine
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia in Low or Intermediate I Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Hematologic improvement as defined by the IWG 2006 criteria [ Time Frame: At least 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to attain hematologic improvement [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Duration of hematologic improvement [ Time Frame: Time to progression/relapse following hematologic improvement, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Bone marrow morphologic response (CR + PR) [ Time Frame: Time to disease progression, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Bone marrow cytogenetic response [ Time Frame: Time to disease progression, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Platelet counts [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Bleeding events [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2012
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • IMiD-1
Drug: Eltrombopag Olamine
Given PO
Other Names:
  • Promacta
  • SB-497115-GR
Other: Laboratory Biomarker Analysis
Correlative studies
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.

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • IMiD-1
Drug: Eltrombopag Olamine
Given PO
Other Names:
  • Promacta
  • SB-497115-GR
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772420

Locations
United States, Kansas
The University of Kansas Recruiting
Lawrence, Kansas, United States, 66047
Contact: Suman Kambhampati    913-588-6029    skambhampati@kumc.edu   
Principal Investigator: Suman Kambhampati         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mrinal M. Patnaik    507-284-3417    Patnaik.mrinal@mayo.edu   
Principal Investigator: Mrinal M. Patnaik         
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Amit K. Verma    718-430-8761    amit.verma@einstein.yu.edu   
Principal Investigator: Amit K. Verma         
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Principal Investigator: Amit Verma Albert Einstein College of Medicine of Yeshiva University
  More Information

No publications provided

Responsible Party: Amit Verma, Principal Investigator, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT01772420     History of Changes
Other Study ID Numbers: 2012-407, NCI-2013-01219, 20-12-407, 12-007, RV--MDS-PI-0645, 115479, 2012-407, P30CA013330
Study First Received: January 15, 2013
Last Updated: March 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Leukemia
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2015