Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00082888
Collaborator
(none)
93
Enrollment
2
Locations
1
Arm
159.4
Actual Duration (Months)
46.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well tipifarnib works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Tipifarnib may be an effective treatment for non-Hodgkin's lymphoma.

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess tumor response to R115777 (tipifarnib) in patients with relapsed aggressive non-Hodgkin's lymphoma. (Permanently closed to accrual 6/28/06) II. To assess tumor response to R115777 in patients with relapsed indolent non-Hodgkin's lymphoma. (Permanently closed to accrual 9/26/07) III. To assess tumor response to R115777 in patients with uncommon non-Hodgkin's lymphomas.

  2. To evaluate toxicity associated with this regimen in patients with relapsed non-Hodgkin's lymphoma.

SECONDARY OBJECTIVES:
  1. To evaluate known and unknown molecular markers that may predict for response to R115777 in lymphoma tissue.
OUTLINE:

Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
93 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Evaluation of FTI (R115777) in Treatment of Relapsed and Refractory Lymphoma
Actual Study Start Date :
Mar 24, 2004
Actual Primary Completion Date :
May 20, 2009
Actual Study Completion Date :
Jul 5, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (tipifarnib)

Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of Participants With Confirmed Response (Complete Response, Unconfirmed Complete Response, or Partial Response) During the First 6 Courses of Treatment [During the first 6 cycles of treatment]

      Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

    Secondary Outcome Measures

    1. Overall Survival [Up to 2 years]

      Overall survival time was defined as the time from registration to the date of death or last follow-up.

    2. Time to Progression [up to 2 years]

      Time to progression was defined as the number of months from registration to the date of disease progression with patients being progression-free being censored on the date of their last evaluation. Progression is defined as ≥50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or nonresponders or appearance of any new lesion during or at the end of therapy.

    3. Duration of Response [up to 2 years]

      Duration of response is defined for all evaluable patients that have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression (PD) is documented. CR:Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy PR:≥50% decrease in SPD of the six largest dominant nodes or nodal masses. PD:≥50 % increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders or appearance of any new lesion during or at the end of therapy.

    4. Number of Patients Who Experienced Grade 3 or 4 Toxicities [Up to 56 days]

      Number of patients that experienced a grade 3 or 4 toxicity (adverse events considered at least possibly related to Tipifarnib) as measured by NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL(Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.). Grade 4: Life-threatening consequences; urgent intervention indicated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Biopsy-proven relapsed or refractory lymphomas; previous biopsies =< 6 months prior to treatment on this protocol will be acceptable as long as there has not been intervening therapy; if the patient has received therapy for non-Hodgkin's disease (NHL) between the time of the last biopsy and this protocol, then a re-biopsy is necessary

    • STUDY 1: Aggressive lymphomas (permanently closed to accrual 6/28/06):

    • Transformed lymphomas

    • Diffuse large B cell lymphoma

    • Mantle cell lymphoma

    • Follicular lymphoma grade III STUDY 2: Indolent lymphomas (permanently closed to accrual 9/26/07)

    • Small lymphocytic lymphoma/chronic lymphocytic leukemia

    • Follicular lymphoma, grades 1, 2

    • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type

    • Nodal marginal zone B-cell lymphoma

    • Splenic marginal zone B-cell lymphoma

    STUDY 3: Uncommon lymphomas:
    • Peripheral T cell lymphoma, unspecified

    • Anaplastic large cell lymphoma (T and null cell type)

    • Lymphoplasmacytic lymphoma

    • Mycosis fungoides/ Sezary syndrome

    • Relapsed Hodgkin's disease (patients must be previously treated and either have had a transplant or not be eligible for a transplant)

    • Previously treated (no limitations on the number of prior therapies); patients with aggressive lymphoma (Study 1 - permanently closed to accrual 6/28/06) should have received or be ineligible for potentially curable therapy including stem cell transplant

    • MEASURABLE DISEASE: Must have at least one lesion that has a single diameter of

    = 2 cm or tumor cells in the blood >= 5 x10^9/L

    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

    • Absolute neutrophil count >=1000/mm^3

    • Platelet count >= 75,000

    • Hemoglobin >= 9 g/dL

    • Total bilirubin =< 2 x upper limit of normal (ULN) (if > 2 x ULN direct bilirubin is required and should be =< 1.5 x ULN)

    • Aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if liver involvement is present)

    • Serum creatinine =< 2 x ULN

    • Expected survival >= 3 months

    • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent

    • Capable of swallowing intact study medication tablets

    • Capable of following directions regarding taking study medication, or has a daily caregiver who will be responsible for administering study medication

    Exclusion Criteria:
    • Any of the following as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women

    • Breastfeeding women

    • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)

    • NOTE: The effects of R115777 on the developing human fetus at the recommended therapeutic dose are unknown

    • Life-threatening illness (unrelated to tumor)

    • Ongoing radiation therapy or radiation therapy =< 3 weeks prior to study registration unless the acute side effects associated with such therapy are resolved

    • Therapy with myelosuppressive chemotherapy, cytotoxic chemotherapy, or biologic therapy =< 3 weeks (6 weeks for nitrosourea or mitomycin C) or corticosteroids =< 2 weeks, prior to starting R11577; patients may be on corticosteroids or tapering off them up until the day they start R11577 as long as it is clear that they are not having a tumor response to the steroids or that the steroids would confuse the interpretation of response to R11577; patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or intractable symptoms of lymphoma

    • Peripheral neuropathy >= grade 3

    • Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives

    • Presence of central nervous system (CNS) lymphoma

    • Other active malignancies

    • Once a patient begins FTI (tipifarnib) treatment, the addition of other cancer treatment will confound the assessment of efficacy and therefore is not allowed; this restriction precludes the addition of cytotoxic, immunologic agents, radiotherapy, or an increase in corticosteroid dose while the patient is in the treatment phase of this protocol

    • Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV patients are excluded because of concerns regarding excess risk of complications of immunosuppressive therapy regimens

    • Known allergy to imidazole drugs such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, sulconazole, tioconazole, or terconazole

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Iowa/Holden Comprehensive Cancer CenterIowa CityIowaUnited States52242
    2Mayo ClinicRochesterMinnesotaUnited States55905

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Thomas E Witzig, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00082888
    Other Study ID Numbers:
    • NCI-2012-02849
    • NCI-2012-02849
    • LS038B
    • LS038B
    • 6246
    • P30CA015083
    • P50CA097274
    First Posted:
    May 19, 2004
    Last Update Posted:
    Apr 13, 2020
    Last Verified:
    Apr 1, 2020

    Study Results

    Participant Flow

    Recruitment DetailsParticipants were recruited from 2 medical clinics in the United States between March 2004 to November 2008.
    Pre-assignment Detail
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Period Title: Overall Study
    STARTED421536
    COMPLETED411536
    NOT COMPLETED100

    Baseline Characteristics

    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma GroupTotal
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Total of all reporting groups
    Overall Participants42153693
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    66.5
    64.0
    48.5
    62
    Sex: Female, Male (Count of Participants)
    Female
    18
    42.9%
    10
    66.7%
    14
    38.9%
    42
    45.2%
    Male
    24
    57.1%
    5
    33.3%
    22
    61.1%
    51
    54.8%

    Outcome Measures

    1. Primary Outcome
    TitleProportion of Participants With Confirmed Response (Complete Response, Unconfirmed Complete Response, or Partial Response) During the First 6 Courses of Treatment
    DescriptionConfirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.
    Time FrameDuring the first 6 cycles of treatment

    Outcome Measure Data

    Analysis Population Description
    All participants are included in this analysis.
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Measure Participants421536
    Number [Proportion of participants]
    0.17
    0.4%
    0.07
    0.5%
    0.31
    0.9%
    2. Secondary Outcome
    TitleOverall Survival
    DescriptionOverall survival time was defined as the time from registration to the date of death or last follow-up.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    All participants are included in this analysis.
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Measure Participants421536
    Median (95% Confidence Interval) [months]
    6.4
    20.6
    19.7
    3. Secondary Outcome
    TitleTime to Progression
    DescriptionTime to progression was defined as the number of months from registration to the date of disease progression with patients being progression-free being censored on the date of their last evaluation. Progression is defined as ≥50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or nonresponders or appearance of any new lesion during or at the end of therapy.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretionPatients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Measure Participants421536
    Median (95% Confidence Interval) [months]
    2.8
    5.2
    3.2
    4. Secondary Outcome
    TitleDuration of Response
    DescriptionDuration of response is defined for all evaluable patients that have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression (PD) is documented. CR:Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy PR:≥50% decrease in SPD of the six largest dominant nodes or nodal masses. PD:≥50 % increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders or appearance of any new lesion during or at the end of therapy.
    Time Frameup to 2 years

    Outcome Measure Data

    Analysis Population Description
    Patients who had a response were included in this analysis.
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Measure Participants7111
    Median (95% Confidence Interval) [months]
    11.3
    2
    7.5
    5. Secondary Outcome
    TitleNumber of Patients Who Experienced Grade 3 or 4 Toxicities
    DescriptionNumber of patients that experienced a grade 3 or 4 toxicity (adverse events considered at least possibly related to Tipifarnib) as measured by NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL(Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.). Grade 4: Life-threatening consequences; urgent intervention indicated.
    Time FrameUp to 56 days

    Outcome Measure Data

    Analysis Population Description
    Only eligible participants are included in this analysis.
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    Measure Participants411536
    Count of Participants [Participants]
    32
    76.2%
    8
    53.3%
    24
    66.7%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Only eligible participants are included in this analysis.
    Arm/Group TitleAggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Arm/Group DescriptionPatients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
    All Cause Mortality
    Aggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total34/41 (82.9%) 9/15 (60%) 27/36 (75%)
    Serious Adverse Events
    Aggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total27/41 (65.9%) 4/15 (26.7%) 20/36 (55.6%)
    Blood and lymphatic system disorders
    Febrile neutropenia3/41 (7.3%) 30/15 (0%) 02/36 (5.6%) 2
    Hemoglobin decreased2/41 (4.9%) 20/15 (0%) 02/36 (5.6%) 2
    Gastrointestinal disorders
    Abdominal pain1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Colonic perforation0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Diarrhea2/41 (4.9%) 20/15 (0%) 01/36 (2.8%) 1
    Gastric ulcer1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Mucositis oral (funct/sympt)1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 1
    Nausea2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Vomiting1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    General disorders
    Death NOS0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Disease progression3/41 (7.3%) 30/15 (0%) 00/36 (0%) 0
    Fatigue7/41 (17.1%) 70/15 (0%) 01/36 (2.8%) 1
    Fever0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pain2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Hepatobiliary disorders
    Cholecystitis1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Infections and infestations
    Bladder infection(unknown ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Colitis, infectious1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Mucosal infection(gr 3/4 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pneumonia(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 03/36 (8.3%) 3
    Sepsis(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Sepsis(gr 3/4 ANC)2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Sinusitis(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Skin infection0/41 (0%) 01/15 (6.7%) 11/36 (2.8%) 1
    Soft tissue infection(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Upper respiratory infectn(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Urinary tract infection(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 3
    Wound infection(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Wound infection(gr 3/4 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Investigations
    Alanine aminotransferase increased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    INR increased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Leukocyte count decreased8/41 (19.5%) 82/15 (13.3%) 37/36 (19.4%) 8
    Lymphocyte count decreased0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Neutrophil count decreased15/41 (36.6%) 173/15 (20%) 49/36 (25%) 12
    Platelet count decreased8/41 (19.5%) 84/15 (26.7%) 58/36 (22.2%) 11
    Metabolism and nutrition disorders
    Blood bicarbonate decreased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Dehydration3/41 (7.3%) 30/15 (0%) 01/36 (2.8%) 1
    Serum calcium increased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Serum magnesium decreased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Serum potassium decreased2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain2/41 (4.9%) 30/15 (0%) 01/36 (2.8%) 1
    Bone pain1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Nervous system disorders
    Ataxia1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Headache1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Mini mental status examination abnormal0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Peripheral motor neuropathy1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Speech disorder1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Psychiatric disorders
    Confusion1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Renal and urinary disorders
    Hemorrhage urinary tract1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Ureteric obstruction1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/41 (2.4%) 10/15 (0%) 04/36 (11.1%) 5
    Pleuritic pain0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pneumonitis1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 1
    Skin and subcutaneous tissue disorders
    Urticaria1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Vascular disorders
    Hypotension4/41 (9.8%) 40/15 (0%) 00/36 (0%) 0
    Other (Not Including Serious) Adverse Events
    Aggressive B-cell NHL GroupIndolent B-cell NHL GroupHL/T-cell Lymphoma Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total38/41 (92.7%) 15/15 (100%) 36/36 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Hemoglobin decreased32/41 (78%) 12114/15 (93.3%) 4326/36 (72.2%) 136
    Cardiac disorders
    Cardiac disorder1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 1
    Palpitations0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Pericardial effusion0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Sinus tachycardia0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Eye disorders
    Flashing vision1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 2
    Vision blurred1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Gastrointestinal disorders
    Abdominal distension0/41 (0%) 00/15 (0%) 01/36 (2.8%) 3
    Abdominal pain3/41 (7.3%) 30/15 (0%) 00/36 (0%) 0
    Ascites1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Cheilitis0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Colitis1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Constipation1/41 (2.4%) 20/15 (0%) 00/36 (0%) 0
    Diarrhea11/41 (26.8%) 165/15 (33.3%) 1412/36 (33.3%) 20
    Dry mouth1/41 (2.4%) 21/15 (6.7%) 30/36 (0%) 0
    Dyspepsia3/41 (7.3%) 31/15 (6.7%) 11/36 (2.8%) 2
    Dysphagia2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Esophagitis0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Flatulence2/41 (4.9%) 20/15 (0%) 04/36 (11.1%) 7
    Gastritis0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Gastrointestinal disorder0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Gastrointestinal pain0/41 (0%) 01/15 (6.7%) 20/36 (0%) 0
    Mucositis oral (funct/sympt)1/41 (2.4%) 11/15 (6.7%) 10/36 (0%) 0
    Nausea8/41 (19.5%) 106/15 (40%) 1612/36 (33.3%) 18
    Oral hemorrhage0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Oral pain0/41 (0%) 01/15 (6.7%) 20/36 (0%) 0
    Periodontal disease0/41 (0%) 01/15 (6.7%) 20/36 (0%) 0
    Rectal fistula0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Vomiting1/41 (2.4%) 13/15 (20%) 52/36 (5.6%) 3
    General disorders
    Chills0/41 (0%) 00/15 (0%) 03/36 (8.3%) 5
    Edema limbs5/41 (12.2%) 61/15 (6.7%) 10/36 (0%) 0
    Fatigue32/41 (78%) 9214/15 (93.3%) 5132/36 (88.9%) 188
    Fever0/41 (0%) 00/15 (0%) 02/36 (5.6%) 4
    General symptom0/41 (0%) 00/15 (0%) 01/36 (2.8%) 2
    Localized edema0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Pain4/41 (9.8%) 50/15 (0%) 00/36 (0%) 0
    Infections and infestations
    Appendicitis perforated0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Bronchitis(gr 0/1/2 ANC)0/41 (0%) 02/15 (13.3%) 51/36 (2.8%) 1
    Catheter related infection(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Infection - Neck(unknown ANC)0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Infection(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 03/36 (8.3%) 3
    Mucosal infection(gr 3/4 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Paranasal sinus infection(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Pleural infection(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pneumonia(gr 0/1/2 ANC)1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 1
    Pneumonia(gr 3/4 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pneumonia(unknown ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Sepsis(gr 0/1/2 ANC)0/41 (0%) 01/15 (6.7%) 11/36 (2.8%) 1
    Sinusitis(gr 0/1/2 ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Sinusitis(gr 3/4 ANC)1/41 (2.4%) 10/15 (0%) 02/36 (5.6%) 2
    Sinusitis(unknown ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Skin infection(unknown ANC)0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Upper respiratory infectn(gr 0/1/2 ANC)2/41 (4.9%) 21/15 (6.7%) 11/36 (2.8%) 1
    Urinary tract infection(gr 3/4 ANC)1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Wound infection1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Injury, poisoning and procedural complications
    Bruising0/41 (0%) 00/15 (0%) 01/36 (2.8%) 4
    Investigations
    Alanine aminotransferase increased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Alkaline phosphatase increased8/41 (19.5%) 311/15 (6.7%) 611/36 (30.6%) 23
    Aspartate aminotransferase increased14/41 (34.1%) 494/15 (26.7%) 98/36 (22.2%) 18
    Blood bilirubin increased5/41 (12.2%) 54/15 (26.7%) 105/36 (13.9%) 7
    CD4 lymphocytes decreased0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Creatinine increased12/41 (29.3%) 585/15 (33.3%) 165/36 (13.9%) 55
    Leukocyte count decreased21/41 (51.2%) 647/15 (46.7%) 2415/36 (41.7%) 36
    Lymphocyte count decreased2/41 (4.9%) 41/15 (6.7%) 41/36 (2.8%) 1
    Neutrophil count decreased17/41 (41.5%) 428/15 (53.3%) 2015/36 (41.7%) 49
    Platelet count decreased29/41 (70.7%) 1238/15 (53.3%) 4323/36 (63.9%) 137
    Weight gain0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Weight loss0/41 (0%) 02/15 (13.3%) 42/36 (5.6%) 3
    Metabolism and nutrition disorders
    Anorexia4/41 (9.8%) 52/15 (13.3%) 63/36 (8.3%) 3
    Blood bicarbonate decreased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Blood glucose increased1/41 (2.4%) 11/15 (6.7%) 20/36 (0%) 0
    Dehydration1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Serum albumin decreased0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Serum calcium decreased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Serum calcium increased1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Serum potassium decreased7/41 (17.1%) 72/15 (13.3%) 24/36 (11.1%) 4
    Serum potassium increased4/41 (9.8%) 50/15 (0%) 00/36 (0%) 0
    Serum sodium decreased6/41 (14.6%) 60/15 (0%) 03/36 (8.3%) 4
    Serum sodium increased2/41 (4.9%) 20/15 (0%) 00/36 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain0/41 (0%) 00/15 (0%) 03/36 (8.3%) 3
    Chest wall pain0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Muscle weakness0/41 (0%) 01/15 (6.7%) 20/36 (0%) 0
    Myalgia1/41 (2.4%) 32/15 (13.3%) 50/36 (0%) 0
    Neck pain0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Pain in extremity1/41 (2.4%) 20/15 (0%) 00/36 (0%) 0
    Nervous system disorders
    Ataxia4/41 (9.8%) 82/15 (13.3%) 33/36 (8.3%) 3
    Dizziness2/41 (4.9%) 23/15 (20%) 42/36 (5.6%) 4
    Dysgeusia0/41 (0%) 01/15 (6.7%) 30/36 (0%) 0
    Extrapyramidal disorder1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Headache2/41 (4.9%) 23/15 (20%) 31/36 (2.8%) 1
    Neurological disorder NOS0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Peripheral motor neuropathy0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Peripheral sensory neuropathy16/41 (39%) 726/15 (40%) 1211/36 (30.6%) 134
    Tremor0/41 (0%) 00/15 (0%) 01/36 (2.8%) 2
    Psychiatric disorders
    Anxiety2/41 (4.9%) 23/15 (20%) 61/36 (2.8%) 1
    Confusion4/41 (9.8%) 41/15 (6.7%) 12/36 (5.6%) 2
    Depression0/41 (0%) 03/15 (20%) 61/36 (2.8%) 3
    Insomnia1/41 (2.4%) 11/15 (6.7%) 22/36 (5.6%) 2
    Libido decreased0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Renal and urinary disorders
    Urinary frequency1/41 (2.4%) 10/15 (0%) 01/36 (2.8%) 1
    Urine discoloration0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Urogenital disorder0/41 (0%) 01/15 (6.7%) 20/36 (0%) 0
    Reproductive system and breast disorders
    Pelvic pain0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Cough1/41 (2.4%) 10/15 (0%) 03/36 (8.3%) 4
    Dyspnea4/41 (9.8%) 53/15 (20%) 33/36 (8.3%) 5
    Epistaxis0/41 (0%) 02/15 (13.3%) 30/36 (0%) 0
    Pleural effusion0/41 (0%) 00/15 (0%) 01/36 (2.8%) 1
    Respiratory disorder0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia2/41 (4.9%) 30/15 (0%) 00/36 (0%) 0
    Dry skin0/41 (0%) 00/15 (0%) 01/36 (2.8%) 13
    Photosensitivity0/41 (0%) 00/15 (0%) 03/36 (8.3%) 18
    Pruritus0/41 (0%) 00/15 (0%) 03/36 (8.3%) 4
    Rash acneiform1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Rash desquamating10/41 (24.4%) 222/15 (13.3%) 413/36 (36.1%) 55
    Skin disorder1/41 (2.4%) 20/15 (0%) 01/36 (2.8%) 1
    Skin ulceration1/41 (2.4%) 10/15 (0%) 00/36 (0%) 0
    Sweating0/41 (0%) 00/15 (0%) 02/36 (5.6%) 3
    Vascular disorders
    Hemorrhage0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0
    Hot flashes0/41 (0%) 00/15 (0%) 01/36 (2.8%) 12
    Hypotension0/41 (0%) 01/15 (6.7%) 10/36 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/TitleThomas E. Witzig, M.D.
    OrganizationMayo Clinic
    Phone507-266-2040
    Emailwitzig@mayo.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00082888
    Other Study ID Numbers:
    • NCI-2012-02849
    • NCI-2012-02849
    • LS038B
    • LS038B
    • 6246
    • P30CA015083
    • P50CA097274
    First Posted:
    May 19, 2004
    Last Update Posted:
    Apr 13, 2020
    Last Verified:
    Apr 1, 2020