Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia

Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
Overall Status
Terminated
CT.gov ID
NCT00867308
Collaborator
(none)
32
Enrollment
1
Location
2
Arms
58
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase II study of lenalidomide in patients with myelodysplastic syndrome (MDS) and with acute myeloid leukemia (AML) with trilineage dysplasia. Patients will receive two cycles of lenalidomide. Patients who respond may given additional cycles of lenalidomide until disease progression.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Lenalidomide 50 mg
  • Drug: Lenalidomide 15 mg
Phase 2

Detailed Description

This is a single center open label phase II study of lenalidomide in IPSS Int-1 with increased blasts or hematologic needs with 5q31.1 deletions who have failed to respond to standard dose lenalidomide., IPSS Int-1 with increased blasts or hematologic needs without 5q31.1 deletions, and Int-2 and high risk myelodysplastic syndrome (MDS) patients with or without 5q31.1 deletions, regardless of whether they have received lenalidomide previously or not. Patients will receive two cycles of 15 mg daily lenalidomide (later amended to 50 mg daily lenalidomide) given on days 1-28 out of a 42 day cycle. Within each of the two cycles of lenalidomide, patients will be given up to three weeks with no drug treatment to recover. Patients who fail to respond after two cycles of treatment may receive two additional cycles if stable. Patients who develop clinical response may continue to receive drug until disease progression.

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia (AML-TLD)
Actual Study Start Date :
Jul 1, 2009
Actual Primary Completion Date :
May 1, 2014
Actual Study Completion Date :
May 1, 2014

Arms and Interventions

ArmIntervention/Treatment
Experimental: Lenalidomide 15 mg

Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.

Drug: Lenalidomide 15 mg
Other Names:
  • Revlimid
  • Experimental: Lenalidomide 50 mg

    Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.

    Drug: Lenalidomide 50 mg
    Other Names:
  • Revlimid
  • Outcome Measures

    Primary Outcome Measures

    1. Response Rate [15 weeks]

      Number of participants with a complete or partial response according to International Working Group 2006 criteria.

    Secondary Outcome Measures

    1. Grade 3-4 Toxicity [Up to 8 months]

      Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age greater than 18 years at the time of signing the informed consent form.

    • Able to adhere to the study visit schedule and other protocol requirements.

    • MDS or MDS/AML

    • Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial

    • ECOG performance status of 0, 1, or 2 at study entry

    • All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of RevAssist®.

    • Patients must have no clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.

    • Subjects must agree to use appropriate contraception.

    Exclusion Criteria:
    • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

    • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).

    • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

    • Use of any other experimental drug or therapy within 21 days of baseline.

    • Known hypersensitivity to thalidomide.

    • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

    • Any prior use of lenalidomide except for MDS patients with del 5q31.1 abnormalities..

    • Concurrent use of other anti-cancer agents or treatments.

    • Patients may not have received prior AML induction chemotherapy or stem cell transplant. However, patients with secondary MDS who have received a stem cell transplant for other indications (eg lymphoma, multiple myeloma) will be eligible.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreMarylandUnited States21205

    Sponsors and Collaborators

    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Investigators

    • Principal Investigator: Amy DeZern, MD, Johns Hopkins University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT00867308
    Other Study ID Numbers:
    • J0882
    • RV- MDS-PI-295
    • NA_00019818
    First Posted:
    Mar 23, 2009
    Last Update Posted:
    Oct 17, 2018
    Last Verified:
    Sep 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail2 participants on the 15mg arm and 3 participants on the 50mg arm were screen failures.
    Arm/Group TitleLenalidomide 15 mgLenalidomide 50 mg
    Arm/Group DescriptionPatients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
    Period Title: Overall Study
    STARTED918
    COMPLETED00
    NOT COMPLETED918

    Baseline Characteristics

    Arm/Group TitleLenalidomide 15 mgLenalidomide 50 mgTotal
    Arm/Group DescriptionPatients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Total of all reporting groups
    Overall Participants91827
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    33.3%
    4
    22.2%
    7
    25.9%
    >=65 years
    6
    66.7%
    14
    77.8%
    20
    74.1%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    77
    70
    72
    Sex: Female, Male (Count of Participants)
    Female
    1
    11.1%
    4
    22.2%
    5
    18.5%
    Male
    8
    88.9%
    14
    77.8%
    22
    81.5%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleResponse Rate
    DescriptionNumber of participants with a complete or partial response according to International Working Group 2006 criteria.
    Time Frame15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleLenalidomide 15 mgLenalidomide 50 mg
    Arm/Group DescriptionPatients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
    Measure Participants918
    Complete response
    0
    0%
    0
    0%
    Partial response
    0
    0%
    2
    11.1%
    2. Secondary Outcome
    TitleGrade 3-4 Toxicity
    DescriptionNumber of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.
    Time FrameUp to 8 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleLenalidomide 15 mgLenalidomide 50 mg
    Arm/Group DescriptionPatients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
    Measure Participants918
    Count of Participants [Participants]
    6
    66.7%
    12
    66.7%

    Adverse Events

    Time FrameUp to 8 months
    Adverse Event Reporting Description Due to significant cytopenias in all participants at presentation and throughout the trial, hematologic toxicity was only reported where bone marrow aplasia lasted for >3 weeks from last dose of lenalidomide with a bone marrow cellularity of <5% without evidence of leukemia. Adverse events were collected weekly throughout the trial.
    Arm/Group TitleLenalidomide 15 mgLenalidomide 50 mg
    Arm/Group DescriptionPatients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression. Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described. Patients without evidence of response after 4 cycles will be taken off-study.
    All Cause Mortality
    Lenalidomide 15 mgLenalidomide 50 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/9 (33.3%) 2/18 (11.1%)
    Serious Adverse Events
    Lenalidomide 15 mgLenalidomide 50 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/9 (33.3%) 9/18 (50%)
    Cardiac disorders
    Hypotension0/9 (0%) 01/18 (5.6%) 1
    General disorders
    Epistaxis1/9 (11.1%) 10/18 (0%) 0
    Infections and infestations
    Clostridium difficile infection0/9 (0%) 01/18 (5.6%) 1
    Endocarditis1/9 (11.1%) 10/18 (0%) 0
    Febrile neutropenia1/9 (11.1%) 11/18 (5.6%) 1
    Fungal pneumonia0/9 (0%) 01/18 (5.6%) 1
    Meningitis1/9 (11.1%) 10/18 (0%) 0
    Pericarditis0/9 (0%) 01/18 (5.6%) 1
    Pneumonia0/9 (0%) 03/18 (16.7%) 3
    Nervous system disorders
    Weakness - leg1/9 (11.1%) 10/18 (0%) 0
    Renal and urinary disorders
    Acute kidney injury0/9 (0%) 01/18 (5.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Hypoxia1/9 (11.1%) 11/18 (5.6%) 1
    Other (Not Including Serious) Adverse Events
    Lenalidomide 15 mgLenalidomide 50 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/9 (77.8%) 13/18 (72.2%)
    Blood and lymphatic system disorders
    Bleeding3/9 (33.3%) 33/18 (16.7%) 5
    Bruising0/9 (0%) 03/18 (16.7%) 3
    Epistaxis4/9 (44.4%) 53/18 (16.7%) 3
    Cardiac disorders
    Atrial fibrillation0/9 (0%) 02/18 (11.1%) 2
    Edema1/9 (11.1%) 17/18 (38.9%) 10
    Lightheadedness0/9 (0%) 02/18 (11.1%) 2
    Gastrointestinal disorders
    Constipation1/9 (11.1%) 16/18 (33.3%) 8
    Diarrhea1/9 (11.1%) 14/18 (22.2%) 7
    Nausea1/9 (11.1%) 11/18 (5.6%) 1
    Stomatitis1/9 (11.1%) 13/18 (16.7%) 3
    Vomiting0/9 (0%) 03/18 (16.7%) 3
    Xerostomia0/9 (0%) 02/18 (11.1%) 2
    General disorders
    Anorexia1/9 (11.1%) 14/18 (22.2%) 4
    Cough3/9 (33.3%) 34/18 (22.2%) 4
    Fatigue5/9 (55.6%) 58/18 (44.4%) 12
    Headache1/9 (11.1%) 21/18 (5.6%) 1
    Hoarseness0/9 (0%) 02/18 (11.1%) 2
    Myalgia0/9 (0%) 06/18 (33.3%) 11
    Pain - back0/9 (0%) 02/18 (11.1%) 2
    Pain - chest1/9 (11.1%) 11/18 (5.6%) 1
    Pain - tooth0/9 (0%) 02/18 (11.1%) 2
    Infections and infestations
    Febrile neutropenia3/9 (33.3%) 31/18 (5.6%) 1
    Fever1/9 (11.1%) 22/18 (11.1%) 2
    Thrush1/9 (11.1%) 11/18 (5.6%) 2
    Investigations
    Anemia2/9 (22.2%) 20/18 (0%) 0
    Hyperbilirubinemia2/9 (22.2%) 21/18 (5.6%) 1
    Hypokalemia1/9 (11.1%) 11/18 (5.6%) 1
    Hyponatremia1/9 (11.1%) 10/18 (0%) 0
    Leukopenia2/9 (22.2%) 20/18 (0%) 0
    Thrombocytopenia3/9 (33.3%) 30/18 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia0/9 (0%) 02/18 (11.1%) 2
    Nervous system disorders
    Confusion1/9 (11.1%) 11/18 (5.6%) 1
    Hallucination0/9 (0%) 02/18 (11.1%) 2
    Neuropathy0/9 (0%) 02/18 (11.1%) 2
    Weakness0/9 (0%) 06/18 (33.3%) 6
    Renal and urinary disorders
    Hematuria0/9 (0%) 02/18 (11.1%) 2
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/9 (11.1%) 13/18 (16.7%) 3
    Skin and subcutaneous tissue disorders
    Pruritis1/9 (11.1%) 28/18 (44.4%) 13
    Rash3/9 (33.3%) 56/18 (33.3%) 9
    Xerosis0/9 (0%) 02/18 (11.1%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAmy DeZern, MD
    OrganizationJohns Hopkins University
    Phone4105027208
    Emailadezern1@jhmi.edu
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT00867308
    Other Study ID Numbers:
    • J0882
    • RV- MDS-PI-295
    • NA_00019818
    First Posted:
    Mar 23, 2009
    Last Update Posted:
    Oct 17, 2018
    Last Verified:
    Sep 1, 2018