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Azacitidine and Lenalidomide for Acute Myeloid Leukemia

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT01016600
Collaborator
Celgene Corporation (Industry)
31
Enrollment
1
Location
4
Arms
54
Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Determine toxicity and remission rates of treatment with azacitidine and lenalidomide for patients with Acute Myeloid Leukemia

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Primary:
Phase 1:

To determine the toxicity and feasibility of combining lenalidomide and azacitidine in patients with relapsed/ refractory AML ≥ 18 years or untreated AML ≥60 years.

Phase 2:

To assess the complete remission (CRm plus CRi) rate after lenalidomide + azacitidine therapy in untreated AML ≥60 years.

Secondary:

  1. To assess the response rate (RR), morphologic leukemia-free state, morphologic complete remission rate (CRm), cytogenetic CR (CRc) rate, CR with incomplete blood counts 14 rate, and partial remission 15 rate (PR).

  2. To assess overall survival (OS) and event free survival (EFS).

  3. To assess time to progression (TTP) in untreated AML ≥60 years.

  4. To assess relapse free survival (RFS) and duration of CR for complete responders.

  5. To determine the incidence and severity of other toxicities of lenalidomide in combination with azacitidine.

  6. Assay the expression levels of cytokines/chemokines in the bone marrow plasma, expression of chemokine receptors/ligands on leukemic blasts important for the AML microenvironment and study the direct cytotoxic effects of lenalidomide, azacitidine and combination of both drugs on cryopreserved AML blast cells.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Trial of Azacitidine Plus Lenalidomide in the Treatment of Acute Myeloid Leukemia
Study Start Date :
Apr 1, 2010
Actual Primary Completion Date :
Nov 1, 2013
Actual Study Completion Date :
Oct 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

Drug: Lenalidomide
Other Names:
  • Revlimid

    • Drug: Azacitidine
    Other Names:
  • Vidaza

    		•
    Experimental: Cohort 2

    Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

    Drug: Lenalidomide
    Other Names:
  • Revlimid

    • Drug: Azacitidine
    Other Names:
  • Vidaza

    		•
    Experimental: Cohort 3

    Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

    Drug: Lenalidomide
    Other Names:
  • Revlimid

    • Drug: Azacitidine
    Other Names:
  • Vidaza

    		•
    Experimental: Phase II

    Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5

    Drug: Lenalidomide
    Other Names:
  • Revlimid

    • Drug: Azacitidine
    Other Names:
  • Vidaza

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I Only - Maximum Tolerated Dose (MTD) as Measured by Dose-limiting Toxicities (DLTs) [Completion of the phase I portion of study (approximately 1 year and 4 months)]

      The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle. Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

    2. Phase I Only - Maximum Tolerated Dose (MTD) [Completion of the phase I portion of study (approximately 1 year and 4 months)]

      The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle. Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

    3. Phase II Only - Complete Remission Rate (CRm + CRi) in Participants With Untreated AML ≥60 Years of Age [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

      Morphologic complete remission (CRm): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.

    Secondary Outcome Measures

    1. Response Rate (CRm + CRc + CRi + PR) [Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]]

      Response rate (CRm + CRc + CRi + PR) CRm = morphologic complete remission CRc = cytogenetic complete remission CRi = morphologic complete remission with incomplete blood count recovery PR = partial remission

    2. Morphologic Leukemia-free State [Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]]

      Defined as < 5% blasts on the BM aspirate with spicules and a count of >200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease.

    3. Morphologic Complete Remission Rate (CRm) [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

      Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.

    4. Cytogenetic CR (CRc) Rate [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

      Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

    5. CR With Incomplete Blood Counts Rate [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

      Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.

    6. Partial Remission Rate (PR) [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

      Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission.

    7. Overall Survival [Until death - median follow-up 4.6 months (full range (0.3-31.4 months))]

      Defined as the date of first dose of study drug to the date of death from any cause.

    8. Event Free Survival [Until death - median follow-up 4.6 months (full range (0.3-31.4 months))]

      Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause.

    9. Time to Progression (TTP) [Until progressive disease - median follow-up 4.6 months (full range (0.3-31.4 months))]

      Defined as the interval from the date of the first dose of study drug to the date of progressive disease.

    10. Relapse Free Survival (RFS) [Until death - median follow-up 4.6 months (full range (0.3-31.4 months))]

      This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause.

    11. Duration of CR for Complete Responders [Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)]

    12. Toxicity Profile (Grade 3/4 Toxicities) [30 days after completion of treatment (median follow-up was 12 weeks (range 8-72 weeks))]

      AML ≥18 years or untreated AML ≥60 years

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Newly diagnosed AML age ≥ 60 years, de novo, secondary to prior therapy, or transformed from MDS, as defined by the International Working Group, except acute promyelocytic leukemia (AML M3) will be included for phase 1 and 2 study. Patients must not have abnormalities of inversion 16, t(16,16), del(16q), t(8,21) or t(15,17) as assessed by routine cytogenetics or FISH. Diagnosis of AML by WHO criteria (>20% blasts) is determined by CBC, bone marrow assessment, and immunophenotypic analysis performed within 2 weeks of study enrollment. No previous treatment for AML, however hydroxyurea, steroids, and leukopheresis are allowed.

    • Relapsed AML age ≥18 years, except acute promyelocytic leukemia (AML M3), with CR < 1 years post 1st induction chemotherapy will be included in phase 1 study only.

    • Primary refractory AML age ≥18 years, except acute promyelocytic leukemia (AML M3) post 1st induction chemotherapy will be included in phase 1 study only.

    • Relapsed or refractory AML age ≥18 years, except acute promyelocytic leukemia (AML M3), post 1st salvage chemotherapy/ autologous stem transplantation/ allogeneic stem cell transplantation will be included in phase 1 study only.

    • Understand and voluntarily sign an informed consent form.

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

    • ECOG performance status of ≤ 2 at study entry

    • Life expectancy > 2 months

    • WBC < 10,000 x 10^6/L (WBC counts may not be reduced by hydroxyurea or leukapheresis to achieve a WBC lower than 10,000 x 106 /L).

    • Adequate renal and hepatic function as defined by:

    • Serum creatinine ≤ 1.5X institution ULN

    • Total bilirubin ≤ 2.0 mg/dL ( except Gilbert's syndrome or known hemolysis)

    • AST(SGOT) and ALT (SGPT) ≤ 2.5 x ULN

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

    • Females of of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

    • Men must agree not to father a child and agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. -Disease free of prior malignancies for ≥ 5 years with exception of AML, currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

    Exclusion Criteria:

    • Newly diagnosed AML age < 60 years.

    • Newly diagnosed AML ≥ 60 years with favorable risk cytogenetic abnormalities as defined by SWOG criteria that include: inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations, t(8;21) lacking del(9q) or complex karyotype 17. Prior to enrollment, FISH studies or routine cytogenetics must be completed to rule out these cytogenetic abnormalities.

    • Known CNS leukemia

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

    • 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 30 days of enrollment.

    • Known hypersensitivity to thalidomide and mannitol.

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

    • Any prior use of lenalidomide

    • Any prior use of azacytidine.

    • Concurrent use of other anti-cancer agents or treatments (with the exception of steroids)

    • Known positive for HIV or infectious hepatitis, type A, B or C.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine St. Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine
    • Celgene Corporation

    Investigators

    • Principal Investigator: Ravi Vij, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01016600
    Other Study ID Numbers:
    • 09-1816 / 201101749
    First Posted:
    Nov 19, 2009
    Last Update Posted:
    Sep 7, 2015
    Last Verified:
    Aug 1, 2015
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Lenalidomide
    Azacitidine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 31 participants were enrolled but only 30 participants started treatment and completed treatment.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Period Title: Overall Study
    STARTED 9 4 6 12
    COMPLETED 8 4 6 12
    NOT COMPLETED 1 0 0 0

    Baseline Characteristics

    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II Total
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Total of all reporting groups
    Overall Participants 9 4 6 12 31
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    70
    67.5
    75.5
    72
    72
    Sex: Female, Male (Count of Participants)
    Female
    6
    66.7%
    1
    25%
    3
    50%
    4
    33.3%
    14
    45.2%
    Male
    3
    33.3%
    3
    75%
    3
    50%
    8
    66.7%
    17
    54.8%
    Region of Enrollment (participants) [Number]
    United States
    9
    100%
    4
    100%
    6
    100%
    12
    100%
    31
    100%

    Outcome Measures

    1. Primary Outcome
    Title Phase I Only - Maximum Tolerated Dose (MTD) as Measured by Dose-limiting Toxicities (DLTs)
    Description The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle. Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.
    Time Frame Completion of the phase I portion of study (approximately 1 year and 4 months)

    Outcome Measure Data

    Analysis Population Description
    (1) participant in Cohort 1 did not start treatment. The Phase II cohort was not analyzed because this was a Phase I outcome only.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 8 4 6 0
    Number [dose-limiting toxicities]
    1
    0
    0
    2. Primary Outcome
    Title Phase I Only - Maximum Tolerated Dose (MTD)
    Description The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle. Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.
    Time Frame Completion of the phase I portion of study (approximately 1 year and 4 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I Cohort
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 18
    Number [mg/m^2]
    75
    3. Secondary Outcome
    Title Response Rate (CRm + CRc + CRi + PR)
    Description Response rate (CRm + CRc + CRi + PR) CRm = morphologic complete remission CRc = cytogenetic complete remission CRi = morphologic complete remission with incomplete blood count recovery PR = partial remission
    Time Frame Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response. (1) participant in Cohort one had both CRm and CRc.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    CRm
    1
    11.1%
    0
    0%
    1
    16.7%
    1
    8.3%
    CRc
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    CRi
    1
    11.1%
    1
    25%
    1
    16.7%
    1
    8.3%
    PR
    2
    22.2%
    0
    0%
    2
    33.3%
    5
    41.7%
    4. Secondary Outcome
    Title Morphologic Leukemia-free State
    Description Defined as < 5% blasts on the BM aspirate with spicules and a count of >200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease.
    Time Frame Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    Number [participants]
    2
    22.2%
    1
    25%
    2
    33.3%
    2
    16.7%
    5. Secondary Outcome
    Title Morphologic Complete Remission Rate (CRm)
    Description Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    Number [participants]
    1
    11.1%
    0
    0%
    1
    16.7%
    1
    8.3%
    6. Secondary Outcome
    Title Cytogenetic CR (CRc) Rate
    Description Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    Number [participants]
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title CR With Incomplete Blood Counts Rate
    Description Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    Number [participants]
    1
    11.1%
    1
    25%
    1
    16.7%
    1
    8.3%
    8. Secondary Outcome
    Title Partial Remission Rate (PR)
    Description Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission.
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    (3) participants in Cohort 1, (1) participant in Cohort 2, and (3) participants in Phase II did not receive 28 days of lenalidomide and therefore are not evaluable for response.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 5 3 6 9
    Number [participants]
    2
    22.2%
    0
    0%
    2
    33.3%
    5
    41.7%
    9. Secondary Outcome
    Title Overall Survival
    Description Defined as the date of first dose of study drug to the date of death from any cause.
    Time Frame Until death - median follow-up 4.6 months (full range (0.3-31.4 months))

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 8 4 6 12
    Median (Full Range) [months]
    4.2
    4.5
    8.9
    4.3
    10. Secondary Outcome
    Title Event Free Survival
    Description Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause.
    Time Frame Until death - median follow-up 4.6 months (full range (0.3-31.4 months))

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 8 4 6 12
    Median (Full Range) [months]
    3.8
    3.4
    7.8
    2.9
    11. Secondary Outcome
    Title Time to Progression (TTP)
    Description Defined as the interval from the date of the first dose of study drug to the date of progressive disease.
    Time Frame Until progressive disease - median follow-up 4.6 months (full range (0.3-31.4 months))

    Outcome Measure Data

    Analysis Population Description
    (2) cohort 1 participants were not evaluable for this outcome measure because (1) was removed for DLT & (1) withdrew from study. (2) phase II participants were not evaluable because both were removed from study in the first cycle for adverse events.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 6 4 6 10
    Median (Full Range) [months]
    5.7
    3.4
    7.8
    3.7
    12. Secondary Outcome
    Title Relapse Free Survival (RFS)
    Description This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause.
    Time Frame Until death - median follow-up 4.6 months (full range (0.3-31.4 months))

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 2 1 2 2
    Median (Full Range) [months]
    12.0
    1.4
    4.9
    12.2
    13. Secondary Outcome
    Title Duration of CR for Complete Responders
    Description
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    (6) participants in Cohort 1, (3) participants in Cohort 2, (4) participants in Cohort 3, and (10) participants in Phase II did not have a complete response and are not evaluable for this outcome.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 2 1 2 2
    Median (Full Range) [months]
    10.9
    1.4
    4.95
    12.15
    14. Secondary Outcome
    Title Toxicity Profile (Grade 3/4 Toxicities)
    Description AML ≥18 years or untreated AML ≥60 years
    Time Frame 30 days after completion of treatment (median follow-up was 12 weeks (range 8-72 weeks))

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 8 4 6 12
    Anemia
    3
    33.3%
    0
    0%
    0
    0%
    4
    33.3%
    Febrile neutropenia
    4
    44.4%
    1
    25%
    3
    50%
    8
    66.7%
    Otitis mastoditis - worsening
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Diarrhea
    1
    11.1%
    0
    0%
    2
    33.3%
    0
    0%
    Nausea
    1
    11.1%
    0
    0%
    0
    0%
    1
    8.3%
    Vomiting
    2
    22.2%
    0
    0%
    0
    0%
    2
    16.7%
    Dental carries
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Fatigue
    1
    11.1%
    0
    0%
    4
    66.7%
    4
    33.3%
    Sepsis
    1
    11.1%
    0
    0%
    2
    33.3%
    1
    8.3%
    Bronchial infection
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Bacteremia
    2
    22.2%
    0
    0%
    1
    16.7%
    0
    0%
    Lung infection
    3
    33.3%
    0
    0%
    2
    33.3%
    9
    75%
    Skin infection
    1
    11.1%
    2
    50%
    2
    33.3%
    2
    16.7%
    Activated partial thromboplastin time prolonged
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Blood bilirubin increased
    2
    22.2%
    0
    0%
    2
    33.3%
    3
    25%
    Creatinine increased
    1
    11.1%
    0
    0%
    1
    16.7%
    0
    0%
    Neutrophil count decreased
    7
    77.8%
    0
    0%
    2
    33.3%
    2
    16.7%
    Platelet count decreased
    4
    44.4%
    2
    50%
    3
    50%
    6
    50%
    White blood cell count decreased
    7
    77.8%
    1
    25%
    4
    66.7%
    10
    83.3%
    Lymphocyte count decreased
    5
    55.6%
    1
    25%
    1
    16.7%
    2
    16.7%
    Dehydration
    2
    22.2%
    0
    0%
    0
    0%
    3
    25%
    Hypernatremia
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Hypocalcemia
    1
    11.1%
    0
    0%
    1
    16.7%
    0
    0%
    Hypophosphatemia
    4
    44.4%
    0
    0%
    3
    50%
    6
    50%
    Back pain
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Generalized muscle weakness
    2
    22.2%
    0
    0%
    1
    16.7%
    2
    16.7%
    Pain in extremity
    1
    11.1%
    0
    0%
    0
    0%
    1
    8.3%
    Leukemia vasculitis left calf
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Acute kidney injury
    1
    11.1%
    0
    0%
    1
    16.7%
    0
    0%
    Dyspnea
    3
    33.3%
    2
    50%
    1
    16.7%
    2
    16.7%
    Epistaxis
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Productive cough
    1
    11.1%
    0
    0%
    1
    16.7%
    0
    0%
    Pulmonary edema
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Rash maculo-papular
    1
    11.1%
    0
    0%
    1
    16.7%
    1
    8.3%
    Skin ulceration
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    Hypotension
    3
    33.3%
    0
    0%
    1
    16.7%
    1
    8.3%
    Constipation
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    Edema limbs
    0
    0%
    1
    25%
    0
    0%
    1
    8.3%
    Catheter related infection
    0
    0%
    1
    25%
    1
    16.7%
    1
    8.3%
    Alanine aminotransferase increased
    0
    0%
    1
    25%
    0
    0%
    1
    8.3%
    INR increased
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    Hyperglycemia
    0
    0%
    1
    25%
    0
    0%
    5
    41.7%
    Hematuria
    0
    0%
    1
    25%
    0
    0%
    1
    8.3%
    Cough
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    Wheezing
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    Cardiac arrest
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Perianal hemorrhage
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Cyst infection
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Incarcerated hernia
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Hypoalbuminemia
    0
    0%
    0
    0%
    1
    16.7%
    1
    8.3%
    Hypokalemia
    0
    0%
    0
    0%
    2
    33.3%
    3
    25%
    Respiratory failure
    0
    0%
    0
    0%
    1
    16.7%
    1
    8.3%
    Pruritus
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Hypertension
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Atrial fibrillation
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Chest pain cardiac
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Left ventricular systolic dysfunction
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Supraventricular tachycardia
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Dysphagia
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Esophagitis
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Lower gastrointestinal hemorrhage
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Pain
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Otitis media
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Scrotal infection
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Upper respiratory infection
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Urinary tract infection
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Wound infection
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Fall
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Fracture
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Weight loss
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Anorexia
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Hyponatremia
    0
    0%
    0
    0%
    0
    0%
    3
    25%
    Neck pain
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Polyarthropathy
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    Syncope
    0
    0%
    0
    0%
    0
    0%
    2
    16.7%
    Pleuritic pain
    0
    0%
    0
    0%
    0
    0%
    2
    16.7%
    15. Primary Outcome
    Title Phase II Only - Complete Remission Rate (CRm + CRi) in Participants With Untreated AML ≥60 Years of Age
    Description Morphologic complete remission (CRm): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.
    Time Frame Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Cohort 1, 2, and 3 were not analyzed for this outcome as it is a Phase II outcome measure only. (3) participants in Phase II cohort were not evaluable for response because they did not complete cycle 1.
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    Measure Participants 0 0 0 9
    Number [percentage of participants]
    22
    244.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Phase II
    Arm/Group Description Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 25 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 50 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5 Induction regimen (total 2 cycles) Lenalidomide 50 mg PO daily days 1-28 Azacitidine 75 mg/m2 (dose determined in Phase I) mg/m2 IV days 1-5 Maintenance Regimen Lenalidomide 10 mg PO daily days 1-28 Azacitidine 75 mg/m2 IV days 1-5
    All Cause Mortality
    Cohort 1 Cohort 2 Cohort 3 Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/8 (100%) 2/4 (50%) 6/6 (100%) 12/12 (100%)
    Blood and lymphatic system disorders
    Anemia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Cardiac disorders
    Cardiac arrest 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Supraventricular tachycardia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Ear and labyrinth disorders
    Otitis media 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Gastrointestinal disorders
    Constipation 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Hemorrhoidal hemorrage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Vomiting 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    General disorders
    Bleeding 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Edema 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Fatigue 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Hernia 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Itching 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Progressive disease 2/8 (25%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Infections and infestations
    Bacteremia blood 2/8 (25%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Catheter related infection 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Cyst infection 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Febrile neutropenia 3/8 (37.5%) 0/4 (0%) 1/6 (16.7%) 3/12 (25%)
    Lung infection 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 9/12 (75%)
    Scrotal infection 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Sepsis 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Injury, poisoning and procedural complications
    Fall 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Fracture 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Post operative hemorrhage (bone marrow biopsy site) 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Investigations
    Thrombocytopenia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Metabolism and nutrition disorders
    Hyperglycemia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hypokalemia 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Nervous system disorders
    Confusion 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Intracranial hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Syncope 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Renal and urinary disorders
    Hematuria 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/8 (0%) 2/4 (50%) 0/6 (0%) 0/12 (0%)
    Respiratory failure 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Skin and subcutaneous tissue disorders
    Skin infection 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Skin ulceration 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Vascular disorders
    Hypotension 3/8 (37.5%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Thromboembolic event DVT 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    Cohort 1 Cohort 2 Cohort 3 Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/8 (100%) 4/4 (100%) 6/6 (100%) 12/12 (100%)
    Blood and lymphatic system disorders
    Anemia 2/8 (25%) 0/4 (0%) 2/6 (33.3%) 4/12 (33.3%)
    Cardiac disorders
    Acute systolic CHF/MV regurgitation 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Atrial flutter 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 4/12 (33.3%)
    Chest pain - cardiac 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Left ventricular systolic dysfunction 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Palpitations 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Pericardial effusion 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Sinus bradycardia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Sinus tachycardia 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 4/12 (33.3%)
    Supraventricular tachycardia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Systolic murmur 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Ear and labyrinth disorders
    Ear pain 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hearing impaired 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Otitis mastoiditis 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Tinnitus 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Vertigo 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Endocrine disorders
    Hypothyroidism 2/8 (25%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Eye disorders
    Blurred vision 0/8 (0%) 0/4 (0%) 0/6 (0%) 3/12 (25%)
    Double vision 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Dry eye 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Eye pain 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Flashing lights 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Visual disturbance/double vision 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Gastrointestinal disorders
    Abdominal pain 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 5/12 (41.7%)
    Constipation 3/8 (37.5%) 1/4 (25%) 1/6 (16.7%) 7/12 (58.3%)
    Dental carries 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Diarrhea 4/8 (50%) 1/4 (25%) 4/6 (66.7%) 7/12 (58.3%)
    Dry mouth 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Dysphagia 2/8 (25%) 0/4 (0%) 1/6 (16.7%) 3/12 (25%)
    Esophagitis 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Gastric hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hemorrhoidal hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hemorrhoids 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Lower gastrointestinal hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Mucositis - oral 2/8 (25%) 1/4 (25%) 2/6 (33.3%) 8/12 (66.7%)
    Nausea 5/8 (62.5%) 3/4 (75%) 5/6 (83.3%) 8/12 (66.7%)
    Oral hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Rectal hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Rectal pain 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Vomiting 3/8 (37.5%) 2/4 (50%) 4/6 (66.7%) 7/12 (58.3%)
    General disorders
    Chills 3/8 (37.5%) 1/4 (25%) 2/6 (33.3%) 7/12 (58.3%)
    Edema face 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Edema limbs 6/8 (75%) 0/4 (0%) 3/6 (50%) 8/12 (66.7%)
    Fatigue 6/8 (75%) 4/4 (100%) 4/6 (66.7%) 9/12 (75%)
    Fever 3/8 (37.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Flu Like Symptoms 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hypothermia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Infusion related reaction 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Malaise 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Non-cardiac chest pain 0/8 (0%) 1/4 (25%) 0/6 (0%) 2/12 (16.7%)
    Pain 3/8 (37.5%) 1/4 (25%) 0/6 (0%) 2/12 (16.7%)
    Perianal hemorrhage 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Hepatobiliary disorders
    Splenomegaly 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Infections and infestations
    Bronchial infection 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Catheter related infection 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Clostridium difficile 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Febrile neutropenia 1/8 (12.5%) 1/4 (25%) 2/6 (33.3%) 5/12 (41.7%)
    Gram positive cocci 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Lip infection 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Lung infection 5/8 (62.5%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Oral thrush 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 4/12 (33.3%)
    Scrotal infection 0/8 (0%) 1/4 (25%) 0/6 (0%) 0/12 (0%)
    Sepsis 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Sinusitis 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Skin infection 3/8 (37.5%) 3/4 (75%) 2/6 (33.3%) 0/12 (0%)
    Staphylococcus epidermis-blood 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Upper respiratory infection 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Urinary tract infection 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    VRE stool 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Vulval infection 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Wound infection 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Injury, poisoning and procedural complications
    Bruising 2/8 (25%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Eye abrasion 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Fall 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Incarcerated hernia 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Perirectal abrasion 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Postoperative hemorrhage 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Vascular access complication 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Investigations
    Activated partial thromboplastin time prolonged 3/8 (37.5%) 0/4 (0%) 1/6 (16.7%) 3/12 (25%)
    Alanine aminotransferase increased 5/8 (62.5%) 3/4 (75%) 3/6 (50%) 9/12 (75%)
    Alkaline phosphatase increased 4/8 (50%) 1/4 (25%) 3/6 (50%) 4/12 (33.3%)
    Aspartate aminotransferase increased 4/8 (50%) 1/4 (25%) 1/6 (16.7%) 6/12 (50%)
    Blood bilirubin increased 4/8 (50%) 0/4 (0%) 4/6 (66.7%) 8/12 (66.7%)
    Cardiac troponin I increased 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Creatinine increased 4/8 (50%) 1/4 (25%) 1/6 (16.7%) 4/12 (33.3%)
    INR increased 2/8 (25%) 1/4 (25%) 1/6 (16.7%) 8/12 (66.7%)
    Lymphocyte count decreased 5/8 (62.5%) 1/4 (25%) 4/6 (66.7%) 9/12 (75%)
    Lymphocyte count increased 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Neutrophil count decreased 7/8 (87.5%) 0/4 (0%) 2/6 (33.3%) 2/12 (16.7%)
    Platelet count decreased 3/8 (37.5%) 2/4 (50%) 3/6 (50%) 7/12 (58.3%)
    Weight gain 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Weight loss 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 5/12 (41.7%)
    White blood cell decreased 7/8 (87.5%) 1/4 (25%) 5/6 (83.3%) 10/12 (83.3%)
    Metabolism and nutrition disorders
    Anorexia 2/8 (25%) 0/4 (0%) 1/6 (16.7%) 5/12 (41.7%)
    Dehydration 4/8 (50%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Hypercalcemia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Hyperglycemia 3/8 (37.5%) 1/4 (25%) 1/6 (16.7%) 4/12 (33.3%)
    Hyperkalemia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 3/12 (25%)
    Hypermagnesemia 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Hypernatremia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Hyperuricemia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Hypoalbuminemia 6/8 (75%) 2/4 (50%) 2/6 (33.3%) 11/12 (91.7%)
    Hypocalcemia 6/8 (75%) 3/4 (75%) 5/6 (83.3%) 11/12 (91.7%)
    Hypoglycemia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hypokalemia 2/8 (25%) 1/4 (25%) 1/6 (16.7%) 7/12 (58.3%)
    Hypomagnesemia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hyponatremia 3/8 (37.5%) 2/4 (50%) 4/6 (66.7%) 7/12 (58.3%)
    Hypophosphatemia 5/8 (62.5%) 1/4 (25%) 3/6 (50%) 7/12 (58.3%)
    Musculoskeletal and connective tissue disorders
    Acute gout attack 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Back pain 1/8 (12.5%) 1/4 (25%) 0/6 (0%) 3/12 (25%)
    Bone pain 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Generalized muscle weakness 5/8 (62.5%) 1/4 (25%) 3/6 (50%) 6/12 (50%)
    Lytic lesion in right parietal bone 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Muscle weakness lower limb 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Neck pain 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Pain in extremity 2/8 (25%) 2/4 (50%) 0/6 (0%) 1/12 (8.3%)
    Polyarthropathy 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukemia vasculitis left calf 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Nervous system disorders
    Delerium 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Dizziness 2/8 (25%) 3/4 (75%) 0/6 (0%) 3/12 (25%)
    Dysgeusia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Facial muscle weakness 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Headache 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Lethargy 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Paresthesia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Presyncope 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Seizure 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Somnolence 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Stroke 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Tremor 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Psychiatric disorders
    Anxiety 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Confusion 2/8 (25%) 0/4 (0%) 2/6 (33.3%) 2/12 (16.7%)
    Depression 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Insomnia 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 2/12 (16.7%)
    Renal and urinary disorders
    Acute kidney injury 1/8 (12.5%) 0/4 (0%) 2/6 (33.3%) 2/12 (16.7%)
    Cystitis noninfective 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hematuria 1/8 (12.5%) 1/4 (25%) 1/6 (16.7%) 6/12 (50%)
    Proteinuria 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 5/12 (41.7%)
    Renal tubular acidosis 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 0/12 (0%)
    Urinary frequency 0/8 (0%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Urinary retention 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Reproductive system and breast disorders
    Scrotal pain 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 3/8 (37.5%) 1/4 (25%) 0/6 (0%) 5/12 (41.7%)
    Cough 2/8 (25%) 2/4 (50%) 1/6 (16.7%) 6/12 (50%)
    Dyspnea 5/8 (62.5%) 1/4 (25%) 4/6 (66.7%) 8/12 (66.7%)
    Epistaxis 2/8 (25%) 0/4 (0%) 1/6 (16.7%) 3/12 (25%)
    Hoarseness 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hypoxia 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 6/12 (50%)
    Nasal congestion 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Pleural effusion 2/8 (25%) 0/4 (0%) 0/6 (0%) 4/12 (33.3%)
    Pleural hemorrhage 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Pleuritic pain 0/8 (0%) 0/4 (0%) 0/6 (0%) 2/12 (16.7%)
    Postnasal drip 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 2/12 (16.7%)
    Productive cough 2/8 (25%) 0/4 (0%) 3/6 (50%) 4/12 (33.3%)
    Pulmonary edema 2/8 (25%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Respiratory failure 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Sore throat 0/8 (0%) 1/4 (25%) 0/6 (0%) 2/12 (16.7%)
    Wheezing 1/8 (12.5%) 1/4 (25%) 0/6 (0%) 1/12 (8.3%)
    Skin and subcutaneous tissue disorders
    Dry skin 1/8 (12.5%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Erythemia 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Pruritus 1/8 (12.5%) 1/4 (25%) 3/6 (50%) 4/12 (33.3%)
    Purpura 0/8 (0%) 0/4 (0%) 0/6 (0%) 6/12 (50%)
    Rash maculo-papular 3/8 (37.5%) 1/4 (25%) 2/6 (33.3%) 7/12 (58.3%)
    Rash-petechial 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Skin hyperpigmentation 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Skin ulceration 0/8 (0%) 1/4 (25%) 0/6 (0%) 3/12 (25%)
    Vascular disorders
    Hematoma 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 1/12 (8.3%)
    Hot flashes 0/8 (0%) 0/4 (0%) 0/6 (0%) 1/12 (8.3%)
    Hypertension 1/8 (12.5%) 0/4 (0%) 1/6 (16.7%) 0/12 (0%)
    Hypotension 0/8 (0%) 0/4 (0%) 1/6 (16.7%) 2/12 (16.7%)
    Thromboembolic event 0/8 (0%) 1/4 (25%) 0/6 (0%) 1/12 (8.3%)

    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/Title Ravi Vij, M.D.
    Organization Washington University School of Medicine
    Phone 314-454-8304
    Email rvij@dom.wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01016600
    Other Study ID Numbers:
    • 09-1816 / 201101749
    First Posted:
    Nov 19, 2009
    Last Update Posted:
    Sep 7, 2015
    Last Verified:
    Aug 1, 2015