Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT01075321
Collaborator
(none)
58
Enrollment
2
Locations
1
Arm
109.1
Actual Duration (Months)
29
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving everolimus together with lenalidomide may be an effective treatment for lymphoma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving everolimus and lenalidomide together and to see how well they work in treating patients with relapsed or refractory non-Hodgkin or Hodgkin lymphoma.

Detailed Description

PRIMARY OBJECTIVES:

I.Phase I: To establish the maximum tolerated dose of EVEROLIMUS and lenalidomide in subjects with relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma.

  1. Phase II: To assess tumor response to EVEROLIMUS and lenalidomide in subjects with relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma.
SECONDARY OBJECTIVES:
  1. To evaluate overall survival, progression-free survival, duration of response, and time to treatment failure of subjects receiving EVEROLIMUS and lenalidomide.

  2. To describe the adverse event profile (using CTCAE CTEP Version 4.0) of EVEROLIMUS and lenalidomide.

OUTLINE: Patients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Study Design

Study Type:
Interventional
Actual Enrollment :
58 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Clinical Trial of the mTor Inhibitor RAD001 (Everolimus) in Combination With Lenalidomide (Revlimid) for Patients With Relapsed or Refractory Lymphoid Malignancy
Actual Study Start Date :
Jan 10, 2011
Actual Primary Completion Date :
Feb 28, 2015
Actual Study Completion Date :
Feb 13, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I

Patients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: everolimus
Given orally
Other Names:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001
  • Drug: lenalidomide
    Given orally
    Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
  • Other: laboratory biomarker analysis
    Correlative studies

    Genetic: polymorphism analysis
    Correlative studies

    Other: immunohistochemistry staining method
    Optional correlative studies
    Other Names:
  • immunohistochemistry
  • Genetic: microarray analysis
    Optional correlative studies
    Other Names:
  • gene expression profiling
  • Genetic: fluorescence in situ hybridization
    Optional correlative studies
    Other Names:
  • fluorescence in situ hybridization (FISH)
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I) [After one 28 day cycle]

      The number of dose-limiting toxic events (DLT) for this combination of drug treatment will determine the Maximum Tolerated Dose (MTD) in subsequent phases of this study. The following events were defined as a DLT: a grade 4+ Neutropenia or platelet count decrease, a grade 4 infection, or any grade 3+ non-hematologic event as assessed using Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. Here, the number of patients reporting a DLT are reported

    2. Best Response to Dose Level 0 [Up to 5 years]

      Patients were assessed using the Cheson et al. Revised Response Criteria for Malignant Lymphoma (Cheson, et al 2007). A Complete Response (CR) was defined as the disappearance of all evidence of disease, no palpable nodules and bone marrow cleared on biopsy. A Partial Response (PR) was defined as regression of measureable disease and no new sites, with a 50% decrease in sum of the products of dimension (SPD) of nodal masses, and no increase in spleen or liver size. Patients with Waldenstrom's Macroglobulinemia were eligible to be evaluated as a Minor Response (MR) in which a reduction between 25% and 50% of serum monoclonal IgM was observed. A Progression (PD) was defined as having any new lesions or a 50% increase in the SPD of any previously involved nodes. A Stable Disease (SD) is the absence of any of the previously defined responses.

    Secondary Outcome Measures

    1. Overall Survival for All Eligible Patients [Up to 5 years]

      Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    2. Progression-Free Survival For All Eligible Patients [Up to 5 years]

      Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.

    3. Duration of Response for All Eligible Patients [Up to 5 years]

      Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest objective status is first noted to be either a CR or PR to the earliest date progression is documented.

    4. Time to Treatment Failure for All Eligible Patients [Up to 5 years]

      Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.

    Eligibility Criteria

    Criteria

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

    Inclusion

    • Histological or cytological confirmation of relapsed or refractory non-Hodgkin lymphoma or Hodgkin lymphoma =< 6 months prior to registration

    • The following disease types are eligible: Study 1 - Aggressive lymphomas- Transformed lymphomas; Diffuse large B cell lymphoma; Mantle cell lymphoma; Follicular lymphoma grade III; Precursor B lymphoblastic leukemia/lymphoma; Mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma/leukemia; Precursor T lymphoblastic leukemia/lymphoma; Primary cutaneous anaplastic large cell lymphoma; and Anaplastic large cell lymphoma-primary systemic type

    • Study 2- Indolent lymphomas: Follicular lymphoma, grades 1, 2; Extranodal marginal zone B-cell lymphoma of MALT type; Nodal marginal zone B-cell lymphoma; Splenic marginal zone B-cell lymphoma; Small lymphocytic lymphoma

    • Study 3- Uncommon lymphomas: Peripheral T cell lymphoma, unspecified; Anaplastic large cell lymphoma (T and null cell type); Lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); Post transplant lymphoproliferative disorders; Mycosis fungoides/Sezary syndrome; Hodgkin Disease; Primary effusion lymphoma; Adult T-cell leukemia/lymphoma; Extranodal NK/T-cell lymphoma, nasal type; Enteropathy-type T-cell lymphoma; Hepatosplenic T-cell lymphoma; Subcutaneous panniculitis-like T-cell lymphoma; Angioimmunoblastic T-cell lymphoma; Anaplastic large cell lymphoma-primary cutaneous type; and Blastic plasmacytoid dendritic cell neoplasm

    • Measurable disease by CT or MRI or PET/CT: Must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x10^9/L (Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler)

    • For lymphoplasmacytic lymphoma patients without measurable lymphadenopathy, measurable disease is defined by both of the following criteria: Bone marrow lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy and quantitative IgM monoclonal protein > 800 mg/dL

    • ANC >= 1200/uL

    • Hgb > 9 g/dl

    • PLT >= 50,000/uL

    • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN the direct bilirubin must be normal

    • AST =< 2.5 x ULN or AST =< 5 x ULN if liver involvement

    • Creatinine =< 1.5 x ULN

    • Creatinine clearance >= 50mL/min (Cockcroft-Gault calculation)

    • Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN (NOTE: Lipid lowering medication is allowed)

    • ECOG Performance Status (PS) 0, 1, or 2

    • Females of childbearing potential (FCBP) must have a negative serum pregnancy test with a sensitivity of at least 50 IU/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, during study treatment and for 8 weeks after the last dose of RAD001 (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)

    • Provide informed written consent

    • Willingness to return to Mayo Clinic enrolling institution for follow-up

    • Patient is willing to provide blood samples for research purposes

    • Recovered from acute side effects of prior myelosuppressive chemotherapy or biological therapy

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

    Exclusion

    • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

    • Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix (If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer)

    • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

    • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; Nursing women; Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 8 weeks after the last dose of study drug (NOTE: If barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception)

    • Patients who have received prior treatment with both an mTOR inhibitor (sirolimus, temsirolimus, everolimus) and lenalidomide who did not have a response to either when used as single agents

    • Patients with a known allergic reaction to thalidomide, RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or their excipients to the point where either agent should not be given again

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

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

    • Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study

    • Immunization with attenuated live vaccines within one week of study entry or during study period

    • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases

    • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

    • Prior Allogeneic Stem Cell Transplant

    • No chronic treatment with systemic steroids or another immunosuppressive agents (at a dose equivalent of greater than 20 mg prednisone per day) or other immunosuppressive agents)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Mayo Clinic in ArizonaScottsdaleArizonaUnited States85259
    2Mayo ClinicRochesterMinnesotaUnited States55905

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Study Chair: Craig Reeder, M.D., Mayo Clinic
    • Principal Investigator: Thomas E. Witzig, M.D., Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT01075321
    Other Study ID Numbers:
    • MC0981
    • NCI-2010-00235
    • 09-003801
    • RV-NHL-HL-PI-0466
    • CRAD001NUS113T
    • MC0981
    First Posted:
    Feb 25, 2010
    Last Update Posted:
    Oct 22, 2020
    Last Verified:
    Sep 1, 2020

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitlePhase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Arm/Group DescriptionPatients receive 5 mg oral everolimus once daily and 5 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 15 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED79933
    COMPLETED69731
    NOT COMPLETED1022

    Baseline Characteristics

    Arm/Group TitleAll Patients (Everolimus and Lenalidomide)
    Arm/Group DescriptionPatients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Overall Participants55
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    62
    Sex: Female, Male (Count of Participants)
    Female
    17
    30.9%
    Male
    38
    69.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    54
    98.2%
    More than one race
    1
    1.8%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    55
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I)
    DescriptionThe number of dose-limiting toxic events (DLT) for this combination of drug treatment will determine the Maximum Tolerated Dose (MTD) in subsequent phases of this study. The following events were defined as a DLT: a grade 4+ Neutropenia or platelet count decrease, a grade 4 infection, or any grade 3+ non-hematologic event as assessed using Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. Here, the number of patients reporting a DLT are reported
    Time FrameAfter one 28 day cycle

    Outcome Measure Data

    Analysis Population Description
    All Phase 1 patients that began treatment, completed 1 cycle, and were evaluated for cycle 1 toxicity were included in this analysis. Of the 9 registered to Dose Level 1, 2 were ineligible for this endpoint (PD before evaluated and dose error) and 1 cancelled. Phase II patients were not evaluated for dose-limiting toxicity.
    Arm/Group TitlePhase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Arm/Group DescriptionPatients receive 5 mg oral everolimus once daily and 5 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 15 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants6960
    Count of Participants [Participants]
    1
    1.8%
    2
    NaN
    3
    NaN
    0
    NaN
    2. Primary Outcome
    TitleBest Response to Dose Level 0
    DescriptionPatients were assessed using the Cheson et al. Revised Response Criteria for Malignant Lymphoma (Cheson, et al 2007). A Complete Response (CR) was defined as the disappearance of all evidence of disease, no palpable nodules and bone marrow cleared on biopsy. A Partial Response (PR) was defined as regression of measureable disease and no new sites, with a 50% decrease in sum of the products of dimension (SPD) of nodal masses, and no increase in spleen or liver size. Patients with Waldenstrom's Macroglobulinemia were eligible to be evaluated as a Minor Response (MR) in which a reduction between 25% and 50% of serum monoclonal IgM was observed. A Progression (PD) was defined as having any new lesions or a 50% increase in the SPD of any previously involved nodes. A Stable Disease (SD) is the absence of any of the previously defined responses.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    All patients that were registered and treated at Dose Level 0 were pooled and included in this endpoint. 9 patients in Phase I and 32 patients in Phase II were treated and evaluable for this endpoint
    Arm/Group TitleDose Level 0
    Arm/Group DescriptionPatients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants41
    Complete Response
    4
    7.3%
    Partial Response
    8
    14.5%
    Minor Response
    1
    1.8%
    Stable Disease
    16
    29.1%
    Progression
    12
    21.8%
    3. Secondary Outcome
    TitleOverall Survival for All Eligible Patients
    DescriptionSurvival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    Fifty-five patients began study treatment and were eligible for response evaluation were pooled and included in this analysis.
    Arm/Group TitleAll Patients (Everolimus and Lenalidomide)
    Arm/Group DescriptionPatients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants55
    Median (95% Confidence Interval) [months]
    20.3
    4. Secondary Outcome
    TitleProgression-Free Survival For All Eligible Patients
    DescriptionProgression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    Fifty-five patients began study treatment and were eligible for response evaluation were pooled and included in this analysis.
    Arm/Group TitleAll Patients (Everolimus and Lenalidomide)
    Arm/Group DescriptionPatients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants55
    Median (95% Confidence Interval) [months]
    5.3
    5. Secondary Outcome
    TitleDuration of Response for All Eligible Patients
    DescriptionDuration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest objective status is first noted to be either a CR or PR to the earliest date progression is documented.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    All eligible patients that began study treatment and evaluated as a CR, PR or MR during treatment were included in this analysis.
    Arm/Group TitleAll Patients (Everolimus and Lenalidomide)
    Arm/Group DescriptionPatients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants15
    Median (95% Confidence Interval) [months]
    14.7
    6. Secondary Outcome
    TitleTime to Treatment Failure for All Eligible Patients
    DescriptionTime to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.
    Time FrameUp to 5 years

    Outcome Measure Data

    Analysis Population Description
    Fifty-five patients began study treatment and were eligible for response evaluation were pooled and included in this analysis.
    Arm/Group TitleAll Patients (Everolimus and Lenalidomide)
    Arm/Group DescriptionPatients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants55
    Median (95% Confidence Interval) [months]
    4.7

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Adverse Events (AEs) were assessed at the end of every 28 day cycle of treatment. Serious AEs and Other (Not Including Serious) AEs summary tables summarizes AEs assessed for participants who did NOT withdraw from the study (i.e. Withdrawal by Subject in participant flow) and did not have protocol violation (i.e. Protocol Violation in participant flow). All-cause mortality is assessed for participants who did NOT withdraw from the study (i.e. Withdrawal by Subject in participant flow).
    Arm/Group TitlePhase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Arm/Group DescriptionPatients receive 5 mg oral everolimus once daily and 5 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 15 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.Patients receive 5 mg oral everolimus once daily and 10 mg oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    Phase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/7 (85.7%) 6/9 (66.7%) 7/8 (87.5%) 18/32 (56.3%)
    Serious Adverse Events
    Phase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/7 (42.9%) 7/9 (77.8%) 5/7 (71.4%) 14/32 (43.8%)
    Blood and lymphatic system disorders
    Febrile neutropenia0/7 (0%) 00/9 (0%) 01/7 (14.3%) 11/32 (3.1%) 1
    Gastrointestinal disorders
    Colitis0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Duodenal obstruction0/7 (0%) 01/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Mucositis oral0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Nausea0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Obstruction gastric0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    General disorders
    Edema limbs1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Fatigue2/7 (28.6%) 20/9 (0%) 01/7 (14.3%) 11/32 (3.1%) 1
    Fever0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Hepatobiliary disorders
    Cholecystitis0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Infections and infestations
    Abdominal infection0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Appendicitis0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Lung infection1/7 (14.3%) 13/9 (33.3%) 30/7 (0%) 00/32 (0%) 0
    Mucosal infection0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Otitis externa0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Otitis media0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Pharyngitis1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Sepsis0/7 (0%) 00/9 (0%) 02/7 (28.6%) 21/32 (3.1%) 1
    Skin infection0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Upper respiratory infection0/7 (0%) 00/9 (0%) 01/7 (14.3%) 11/32 (3.1%) 1
    Investigations
    Electrocardiogram QT corrected interval prolonged0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Lymphocyte count decreased0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Neutrophil count decreased1/7 (14.3%) 13/9 (33.3%) 32/7 (28.6%) 25/32 (15.6%) 5
    Platelet count decreased1/7 (14.3%) 12/9 (22.2%) 21/7 (14.3%) 13/32 (9.4%) 4
    Weight loss0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    White blood cell decreased1/7 (14.3%) 13/9 (33.3%) 31/7 (14.3%) 13/32 (9.4%) 3
    Metabolism and nutrition disorders
    Anorexia0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Dehydration1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Hypertriglyceridemia0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify0/7 (0%) 01/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Nervous system disorders
    Seizure0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Syncope0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Skin and subcutaneous tissue disorders
    Rash acneiform0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Vascular disorders
    Thromboembolic event0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Other (Not Including Serious) Adverse Events
    Phase I: Dose Level -1Phase I: Dose Level 0Phase I: Dose Level 1Phase II: Dose Level 0
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/7 (85.7%) 9/9 (100%) 7/7 (100%) 32/32 (100%)
    Blood and lymphatic system disorders
    Anemia1/7 (14.3%) 14/9 (44.4%) 122/7 (28.6%) 28/32 (25%) 27
    Blood and lymphatic system disorders - Other, specify0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Febrile neutropenia1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Ear and labyrinth disorders
    Ear pain0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    External ear inflammation0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Endocrine disorders
    Hypothyroidism0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 3
    Gastrointestinal disorders
    Ascites1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Diarrhea3/7 (42.9%) 56/9 (66.7%) 90/7 (0%) 017/32 (53.1%) 61
    Gastroesophageal reflux disease0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Gastrointestinal disorders - Other, specify0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Mucositis oral2/7 (28.6%) 32/9 (22.2%) 62/7 (28.6%) 36/32 (18.8%) 15
    Nausea3/7 (42.9%) 54/9 (44.4%) 94/7 (57.1%) 517/32 (53.1%) 39
    Toothache0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Vomiting2/7 (28.6%) 23/9 (33.3%) 53/7 (42.9%) 39/32 (28.1%) 12
    General disorders
    Chills1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Edema face1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Edema limbs3/7 (42.9%) 115/9 (55.6%) 232/7 (28.6%) 213/32 (40.6%) 32
    Fatigue6/7 (85.7%) 227/9 (77.8%) 387/7 (100%) 1127/32 (84.4%) 178
    Fever1/7 (14.3%) 20/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Pain0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Immune system disorders
    Allergic reaction0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Infections and infestations
    Infections and infestations - Other, specify0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Lung infection0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Mucosal infection1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Peripheral nerve infection1/7 (14.3%) 10/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Pharyngitis0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Pleural infection0/7 (0%) 01/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Rhinitis infective0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Skin infection0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Tooth infection0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 2
    Upper respiratory infection0/7 (0%) 00/9 (0%) 00/7 (0%) 02/32 (6.3%) 3
    Investigations
    Alkaline phosphatase increased1/7 (14.3%) 11/9 (11.1%) 10/7 (0%) 02/32 (6.3%) 2
    Blood bilirubin increased0/7 (0%) 01/9 (11.1%) 10/7 (0%) 01/32 (3.1%) 2
    CD4 lymphocytes decreased0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Cholesterol high1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    INR increased0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Lymphocyte count decreased0/7 (0%) 00/9 (0%) 01/7 (14.3%) 610/32 (31.3%) 32
    Neutrophil count decreased3/7 (42.9%) 128/9 (88.9%) 434/7 (57.1%) 1425/32 (78.1%) 159
    Platelet count decreased3/7 (42.9%) 169/9 (100%) 685/7 (71.4%) 1523/32 (71.9%) 140
    Weight loss0/7 (0%) 00/9 (0%) 00/7 (0%) 02/32 (6.3%) 8
    White blood cell decreased4/7 (57.1%) 188/9 (88.9%) 526/7 (85.7%) 1726/32 (81.3%) 137
    Metabolism and nutrition disorders
    Anorexia1/7 (14.3%) 10/9 (0%) 01/7 (14.3%) 12/32 (6.3%) 3
    Dehydration1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Hyperglycemia1/7 (14.3%) 10/9 (0%) 00/7 (0%) 02/32 (6.3%) 2
    Hypertriglyceridemia1/7 (14.3%) 30/9 (0%) 01/7 (14.3%) 12/32 (6.3%) 7
    Hypokalemia0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 2
    Hyponatremia1/7 (14.3%) 11/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Nervous system disorders
    Dizziness0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Dysgeusia0/7 (0%) 01/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Syncope0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Renal and urinary disorders
    Urinary tract obstruction0/7 (0%) 00/9 (0%) 01/7 (14.3%) 10/32 (0%) 0
    Reproductive system and breast disorders
    Reproductive system and breast disorders - Other, specify0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 2
    Cough4/7 (57.1%) 126/9 (66.7%) 185/7 (71.4%) 723/32 (71.9%) 67
    Dyspnea5/7 (71.4%) 96/9 (66.7%) 132/7 (28.6%) 317/32 (53.1%) 52
    Pneumonitis1/7 (14.3%) 20/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Pulmonary edema1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Sore throat1/7 (14.3%) 11/9 (11.1%) 10/7 (0%) 01/32 (3.1%) 1
    Skin and subcutaneous tissue disorders
    Bullous dermatitis0/7 (0%) 00/9 (0%) 00/7 (0%) 01/32 (3.1%) 2
    Rash acneiform4/7 (57.1%) 82/9 (22.2%) 23/7 (42.9%) 318/32 (56.3%) 43
    Rash maculo-papular0/7 (0%) 01/9 (11.1%) 10/7 (0%) 00/32 (0%) 0
    Vascular disorders
    Hypertension1/7 (14.3%) 10/9 (0%) 00/7 (0%) 00/32 (0%) 0
    Thromboembolic event0/7 (0%) 01/9 (11.1%) 11/7 (14.3%) 11/32 (3.1%) 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/TitleCraig B. Reeder MD
    OrganizationMayo Clinic
    Phone480.301.8000
    EmailReeder.Craig@mayo.edu
    Responsible Party:
    Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT01075321
    Other Study ID Numbers:
    • MC0981
    • NCI-2010-00235
    • 09-003801
    • RV-NHL-HL-PI-0466
    • CRAD001NUS113T
    • MC0981
    First Posted:
    Feb 25, 2010
    Last Update Posted:
    Oct 22, 2020
    Last Verified:
    Sep 1, 2020