Busulfan, Etoposide, and Intensity-Modulated Radiation Therapy Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Myeloid Cancer

Sponsor
City of Hope Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00540995
Collaborator
(none)
25
1
2
49.9
0.5

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy drugs, such as busulfan and etoposide, and intensity-modulated radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving intensity-modulated radiation therapy together with busulfan and etoposide before a transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of intensity-modulated radiation therapy when given together with busulfan and etoposide followed by a donor stem cell transplant and to see how well it works in treating patients with advanced myeloid cancer.

Detailed Description

OBJECTIVES:
  1. To establish the maximum tolerated dose (MTD) of a large field image-guided IMRT, using helical tomotherapy, when given in combination with IV busulfan and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling in patients with advanced myeloid malignancies. (Phase I) II. To describe the toxicities at each dose level studied. (Phase I) III. To estimate the radiation doses to the whole body, normal organs, and bone marrow through serial imaging studies following the administration of IMRT. (Phase I) IV. To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this preparative regimen. (Phase II) V. To characterize the treatment related mortality and toxicity profile (early/late) associated with this regimen. (Phase II) VI. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population conditioned with whole-body radiotherapy. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy followed by a phase II study.

PREPARATIVE CHEMOTHERAPY: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.

After completion of study treatment, patients are followed periodically for 1 year and then annually for 2 years thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Study of Intravenous (IV) Busulfan and Etoposide (VP-16) Combined With Escalated Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Advanced Myeloid Malignancies
Actual Study Start Date :
Jun 11, 2007
Actual Primary Completion Date :
May 17, 2011
Actual Study Completion Date :
Aug 9, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I: 1200cGy

1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate.

Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
  • Drug: etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • epipodophyllotoxin
  • VePesid
  • VP-16
  • VP-16-213
  • Radiation: intensity-modulated radiation therapy
    Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Other Names:
  • IMRT
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy

    Procedure: allogeneic bone marrow transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy
    Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
  • Procedure: peripheral blood stem cell transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy
    Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
  • Radiation: tomotherapy
    Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Other Names:
  • helical tomotherapy
  • Experimental: Arm II: 1350cGy

    1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5.

    Drug: busulfan
    Given IV
    Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
  • Drug: etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • epipodophyllotoxin
  • VePesid
  • VP-16
  • VP-16-213
  • Radiation: intensity-modulated radiation therapy
    Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Other Names:
  • IMRT
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy

    Procedure: allogeneic bone marrow transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy
    Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
  • Procedure: peripheral blood stem cell transplantation
    Stem cell transplantation occurs on Day 0 after High Dose Therapy
    Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
  • Radiation: tomotherapy
    Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Other Names:
  • helical tomotherapy
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Intensity-modulated Radiation Therapy (Phase I) [from initial treatment date to Day 30 post-transplant]

      The highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study treatment when at least six patients were treated at the dose and are evaluable for toxicity. The MDT is one dose level below the DLT level. At least six patients will be treated at the MTD.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion

    • Patients with the following diagnoses are eligible for this study: Advanced myeloid malignancy with a disease status of more than second remission, induction failure, or relapse; Chronic myeloid leukemia in blast crisis; Myelodysplasia, specifically refractory anemia with excess blasts (RAEB)

    • All candidates for this study must have a HLA (-A, -B, -C, -DR) identical sibling who is willing to donate bone marrow or primed blood stem cells or a 10/10 allele-matched unrelated donor or minor mismatches as per BMT SOP that allows Tacrolimus and Sirolimus to be given for GVH prophylaxis; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)

    • Prior therapy with VP-16, busulfan, hydrea and gleevec are allowed

    • A cardiac evaluation with electrocardiogram and MUGA or echocardiogram is required for all patients; patients must have an ejection fracture of greater than or equal to 50%

    • Patients must have a serum creatinine of less than or equal to 1.2 or creatinine clearance > 80 ml/min

    • A bilirubin of less than or equal to 1.5; patients should also have an SGOT and SGPT less than 5 times the upper limit of normal

    • Pulmonary function tests including DLCO will be performed; FEV1 and DLCO should be greater than 50% of predicted normal value

    • Time from the end of last induction or reinduction attempt should be greater than or equal to 21 days

    • A signed (IRB approved) informed consent document is required; the patient, donor family member, and transplant team (physician, nurse, and social worker) meet together at least once prior to starting the transplant procedure to review all pertinent risk/benefit information as part of the consenting process; alternative treatment modalities are also discussed at this meeting

    Exclusion

    • Prior radiation therapy/exposure that prevents patient from receiving IMRT (Determination will be made by the Radiation Oncologist)

    • Patients who have previously undergone a blood/marrow transplant and now have relapsed disease

    • Patients with a psychological or medical condition that the treating physician deems unacceptable to proceed to allogeneic bone marrow transplant

    • Pregnancy

    • EKG showing ischemic changes or abnormal rhythm and echocardiogram showing ejection fraction < 50 % or abnormal wall motion

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010

    Sponsors and Collaborators

    • City of Hope Medical Center

    Investigators

    • Principal Investigator: Anthony Stein, City of Hope Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT00540995
    Other Study ID Numbers:
    • 05013
    • NCI-2010-00354
    • CDR0000567452
    First Posted:
    Oct 8, 2007
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I: 1200cGy Arm II: 1350cGy
    Arm/Group Description 1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses 1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Period Title: Overall Study
    STARTED 23 2
    COMPLETED 23 2
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Arm I: 1200cGy Arm II: 1350cGy Total
    Arm/Group Description 1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses 1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses Total of all reporting groups
    Overall Participants 23 2 25
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    40
    36
    40
    Sex: Female, Male (Count of Participants)
    Female
    9
    39.1%
    1
    50%
    10
    40%
    Male
    14
    60.9%
    1
    50%
    15
    60%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    21.7%
    1
    50%
    6
    24%
    Not Hispanic or Latino
    17
    73.9%
    1
    50%
    18
    72%
    Unknown or Not Reported
    1
    4.3%
    0
    0%
    1
    4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    4.3%
    0
    0%
    1
    4%
    Native Hawaiian or Other Pacific Islander
    1
    4.3%
    0
    0%
    1
    4%
    Black or African American
    1
    4.3%
    0
    0%
    1
    4%
    White
    19
    82.6%
    2
    100%
    21
    84%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    4.3%
    0
    0%
    1
    4%
    Region of Enrollment (participants) [Number]
    United States
    23
    100%
    2
    100%
    25
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of Intensity-modulated Radiation Therapy (Phase I)
    Description The highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study treatment when at least six patients were treated at the dose and are evaluable for toxicity. The MDT is one dose level below the DLT level. At least six patients will be treated at the MTD.
    Time Frame from initial treatment date to Day 30 post-transplant

    Outcome Measure Data

    Analysis Population Description
    6 patients treated at dose level one (1200cGy) are evaluable for dose limiting evaluable in Phase I.
    Arm/Group Title Arm I: 1200cGy
    Arm/Group Description 1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    Measure Participants 6
    Number [cGy]
    1200

    Adverse Events

    Time Frame Adverse events were captured from initial treatment to Day 180 post-transplant. Vital Statuses were captured from the initial treatment to death.
    Adverse Event Reporting Description
    Arm/Group Title Arm I: 1200cGy Arm II: 1350cGy
    Arm/Group Description 1200cGy = 150cGy x 8 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses 1350cGy = 150cGy x 9 doses: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. busulfan: Given IV etoposide: Given IV intensity-modulated radiation therapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses allogeneic hematopoietic stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy allogeneic bone marrow transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy peripheral blood stem cell transplantation: Stem cell transplantation occurs on Day 0 after High Dose Therapy tomotherapy: Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
    All Cause Mortality
    Arm I: 1200cGy Arm II: 1350cGy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/23 (82.6%) 2/2 (100%)
    Serious Adverse Events
    Arm I: 1200cGy Arm II: 1350cGy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/23 (30.4%) 2/2 (100%)
    Cardiac disorders
    Pericarditis 1/23 (4.3%) 1 0/2 (0%) 0
    Gastrointestinal disorders
    Ascites (non-malignant) 1/23 (4.3%) 1 0/2 (0%) 0
    Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) 0/23 (0%) 0 1/2 (50%) 1
    Mucositis/stomatitis (clinical exam) 0/23 (0%) 0 1/2 (50%) 1
    Mucositis/stomatitis (functional/symptomatic) 0/23 (0%) 0 1/2 (50%) 1
    Infections and infestations
    Colitis, infectious (e.g., Clostridium difficile) 1/23 (4.3%) 1 0/2 (0%) 0
    Febrile neutropenia (ANC <1.0 x 10e9/L, fever >=38.5 degrees C) 1/23 (4.3%) 1 0/2 (0%) 0
    Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) 2/23 (8.7%) 2 0/2 (0%) 0
    Investigations
    Syndromes - Other (Specify, __) 1/23 (4.3%) 1 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult Respiratory Distress Syndrome (ARDS) 1/23 (4.3%) 1 0/2 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm I: 1200cGy Arm II: 1350cGy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/23 (100%) 2/2 (100%)
    Blood and lymphatic system disorders
    Hemoglobin 22/23 (95.7%) 22 1/2 (50%) 1
    Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis) 0/23 (0%) 0 1/2 (50%) 1
    Iron overload 1/23 (4.3%) 1 0/2 (0%) 0
    Leukocytes (total WBC) 21/23 (91.3%) 21 2/2 (100%) 2
    Lymphopenia 22/23 (95.7%) 22 2/2 (100%) 2
    Neutrophils/granulocytes (ANC/AGC) 20/23 (87%) 20 2/2 (100%) 2
    Platelets 22/23 (95.7%) 22 2/2 (100%) 2
    Transfusion: Platelets for BMT studies, if specified in the protocol. 1/23 (4.3%) 1 2/2 (100%) 2
    Transfusion: pRBCs for BMT studies, if specified in the protocol. 1/23 (4.3%) 1 2/2 (100%) 2
    Cardiac disorders
    Supraventricular and nodal arrhythmia 22/23 (95.7%) 22 2/2 (100%) 2
    Hypertension 9/23 (39.1%) 9 1/2 (50%) 1
    Hypotension 8/23 (34.8%) 8 2/2 (100%) 2
    Left ventricular systolic dysfunction 1/23 (4.3%) 1 0/2 (0%) 0
    Myocarditis 1/23 (4.3%) 1 0/2 (0%) 0
    Pericardial effusion (non-malignant) 2/23 (8.7%) 2 0/2 (0%) 0
    Pericarditis 1/23 (4.3%) 1 0/2 (0%) 0
    Restrictive cardiomyopathy 1/23 (4.3%) 1 0/2 (0%) 0
    Valvular heart disease 1/23 (4.3%) 1 0/2 (0%) 0
    Eye disorders
    Dry eye syndrome 8/23 (34.8%) 8 1/2 (50%) 1
    Ocular/Visual - Other (Specify, __) 1/23 (4.3%) 1 0/2 (0%) 0
    Vision-blurred vision 1/23 (4.3%) 1 0/2 (0%) 0
    Gastrointestinal disorders
    Anorexia 16/23 (69.6%) 16 1/2 (50%) 1
    Ascites (non-malignant) 2/23 (8.7%) 2 1/2 (50%) 1
    Colitis 1/23 (4.3%) 1 0/2 (0%) 0
    Constipation 8/23 (34.8%) 8 2/2 (100%) 2
    Dehydration 1/23 (4.3%) 1 0/2 (0%) 0
    Diarrhea 19/23 (82.6%) 19 2/2 (100%) 2
    Distension/bloating, abdominal 13/23 (56.5%) 13 2/2 (100%) 2
    Dry mouth/salivary gland (xerostomia) 3/23 (13%) 3 1/2 (50%) 1
    Esophagitis 4/23 (17.4%) 4 0/2 (0%) 0
    Flatulence 5/23 (21.7%) 5 1/2 (50%) 1
    Gastrointestinal - Other (Specify, __) 1/23 (4.3%) 1 0/2 (0%) 0
    Heartburn/dyspepsia 12/23 (52.2%) 12 1/2 (50%) 1
    Hemorrhoids 6/23 (26.1%) 6 1/2 (50%) 1
    Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) 1/23 (4.3%) 1 0/2 (0%) 0
    Incontinence, anal 3/23 (13%) 3 0/2 (0%) 0
    Mucositis/stomatitis (clinical exam) 22/23 (95.7%) 22 1/2 (50%) 1
    Mucositis/stomatitis (functional/symptomatic) 22/23 (95.7%) 22 1/2 (50%) 1
    Nausea 23/23 (100%) 23 2/2 (100%) 2
    Proctitis 2/23 (8.7%) 2 0/2 (0%) 0
    Taste alteration (dysgeusia) 4/23 (17.4%) 4 0/2 (0%) 0
    Typhlitis (cecal inflammation) 1/23 (4.3%) 1 0/2 (0%) 0
    Vomiting 22/23 (95.7%) 22 2/2 (100%) 2
    General disorders
    Fatigue (asthenia, lethargy, malaise) 23/23 (100%) 23 2/2 (100%) 2
    Fever (in the absence of neutropenia, ANC <1.0 x 10e9/L) 8/23 (34.8%) 8 0/2 (0%) 0
    Insomnia 18/23 (78.3%) 18 0/2 (0%) 0
    Rigors/chills 16/23 (69.6%) 16 2/2 (100%) 2
    Sweating (diaphoresis) 2/23 (8.7%) 2 0/2 (0%) 0
    Weight gain 11/23 (47.8%) 11 1/2 (50%) 1
    Weight gain 0/23 (0%) 0 1/2 (50%) 1
    Weight loss 10/23 (43.5%) 10 0/2 (0%) 0
    Edema:head and neck 11/23 (47.8%) 11 1/2 (50%) 1
    Edema:limb 21/23 (91.3%) 21 2/2 (100%) 2
    Edema:trunk/genital 7/23 (30.4%) 7 0/2 (0%) 0
    Pain 23/23 (100%) 23 2/2 (100%) 2
    Hepatobiliary disorders
    Cholecystitis 1/23 (4.3%) 1 0/2 (0%) 0
    Hepatobiliary/Pancreas - Other (Specify, __) 1/23 (4.3%) 1 0/2 (0%) 0
    Liver dysfunction/failure (clinical) 2/23 (8.7%) 2 0/2 (0%) 0
    Immune system disorders
    Allergic reaction/hypersensitivity (including drug fever) 4/23 (17.4%) 4 1/2 (50%) 1
    Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) 4/23 (17.4%) 4 0/2 (0%) 0
    Infections and infestations
    Febrile neutropenia (ANC <1.0 x 10e9/L, fever >=38.5 degrees C) 13/23 (56.5%) 13 1/2 (50%) 1
    Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) 13/23 (56.5%) 13 2/2 (100%) 2
    Infection with normal ANC or Grade 1 or 2 neutrophils 5/23 (21.7%) 5 1/2 (50%) 1
    Opportunistic infection associated with >=Grade 2 Lymphopenia 1/23 (4.3%) 1 1/2 (50%) 1
    Infection, Bacterial (COH) 2/23 (8.7%) 2 0/2 (0%) 0
    Infection, Fungal (COH) 1/23 (4.3%) 1 0/2 (0%) 0
    Investigations
    Veno-Occlusive Disease (VOD) 0/23 (0%) 0 1/2 (50%) 1
    ALT, SGPT (serum glutamic pyruvic transaminase) 16/23 (69.6%) 16 1/2 (50%) 1
    AST, SGOT(serum glutamic oxaloacetic transaminase) 20/23 (87%) 20 2/2 (100%) 2
    Acidosis (metabolic or respiratory) 0/23 (0%) 0 1/2 (50%) 1
    Albumin, serum-low (hypoalbuminemia) 21/23 (91.3%) 21 2/2 (100%) 2
    Alkaline phosphatase 20/23 (87%) 20 2/2 (100%) 2
    Alkalosis (metabolic or respiratory) 3/23 (13%) 3 0/2 (0%) 0
    Bicarbonate, serum-low 15/23 (65.2%) 15 1/2 (50%) 1
    Bilirubin (hyperbilirubinemia) 9/23 (39.1%) 9 2/2 (100%) 2
    CPK (creatine phosphokinase) 1/23 (4.3%) 1 0/2 (0%) 0
    Syndromes - Other (Specify, __) 4/23 (17.4%) 4 0/2 (0%) 0
    Tumor lysis syndrome 1/23 (4.3%) 1 0/2 (0%) 0
    Metabolism and nutrition disorders
    Calcium, serum-high (hypercalcemia) 6/23 (26.1%) 6 0/2 (0%) 0
    Calcium, serum-low (hypocalcemia) 21/23 (91.3%) 21 2/2 (100%) 2
    Cholesterol, serum-high (hypercholesteremia) 5/23 (21.7%) 5 0/2 (0%) 0
    Creatinine 7/23 (30.4%) 7 2/2 (100%) 2
    Glucose, serum-high (hyperglycemia) 21/23 (91.3%) 21 2/2 (100%) 2
    Glucose, serum-low (hypoglycemia) 1/23 (4.3%) 1 0/2 (0%) 0
    Magnesium, serum-high (hypermagnesemia) 7/23 (30.4%) 7 2/2 (100%) 2
    Magnesium, serum-low (hypomagnesemia) 21/23 (91.3%) 21 2/2 (100%) 2
    Phosphate, serum-low (hypophosphatemia) 19/23 (82.6%) 19 2/2 (100%) 2
    Potassium, serum-high (hyperkalemia) 6/23 (26.1%) 6 1/2 (50%) 1
    Potassium, serum-low (hypokalemia) 21/23 (91.3%) 21 2/2 (100%) 2
    Proteinuria 4/23 (17.4%) 4 0/2 (0%) 0
    Sodium, serum-high (hypernatremia) 7/23 (30.4%) 7 1/2 (50%) 1
    Sodium, serum-low (hyponatremia) 22/23 (95.7%) 22 2/2 (100%) 2
    Triglyceride, serum-high (hypertriglyceridemia) 20/23 (87%) 20 1/2 (50%) 1
    Uric acid, serum-high (hyperuricemia) 5/23 (21.7%) 5 0/2 (0%) 0
    Musculoskeletal and connective tissue disorders
    Muscle weakness, generalized or specific area (not due to neuropathy) 13/23 (56.5%) 13 1/2 (50%) 1
    Musculoskeletal/Soft Tissue - Other (Specify, __) 1/23 (4.3%) 1 1/2 (50%) 1
    Nervous system disorders
    Confusion 9/23 (39.1%) 9 2/2 (100%) 2
    Dizziness 4/23 (17.4%) 4 0/2 (0%) 0
    Mood alteration 21/23 (91.3%) 21 2/2 (100%) 2
    Neuropathy: cranial 1/23 (4.3%) 1 0/2 (0%) 0
    Neuropathy: motor 2/23 (8.7%) 2 0/2 (0%) 0
    Neuropathy: sensory 3/23 (13%) 3 1/2 (50%) 1
    Somnolence/depressed level of consciousness 4/23 (17.4%) 4 0/2 (0%) 0
    Tremor 6/23 (26.1%) 6 0/2 (0%) 0
    Renal and urinary disorders
    Cystitis 1/23 (4.3%) 1 0/2 (0%) 0
    Incontinence, urinary 3/23 (13%) 3 1/2 (50%) 1
    Renal failure 5/23 (21.7%) 5 0/2 (0%) 0
    Renal/Genitourinary - Other (Specify, __) 2/23 (8.7%) 2 1/2 (50%) 1
    Urinary frequency/urgency 1/23 (4.3%) 1 0/2 (0%) 0
    Urinary retention (including neurogenic bladder) 1/23 (4.3%) 1 0/2 (0%) 0
    Urine color change 3/23 (13%) 3 0/2 (0%) 0
    Reproductive system and breast disorders
    Vaginal discharge (non-infectious) 0/23 (0%) 0 1/2 (50%) 1
    Vaginitis (not due to infection) 1/23 (4.3%) 1 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult Respiratory Distress Syndrome (ARDS) 1/23 (4.3%) 1 0/2 (0%) 0
    Atelectasis 8/23 (34.8%) 8 1/2 (50%) 1
    Cough 15/23 (65.2%) 15 0/2 (0%) 0
    Dyspnea (shortness of breath) 10/23 (43.5%) 10 2/2 (100%) 2
    FEV(1) 1/23 (4.3%) 1 0/2 (0%) 0
    Hiccoughs (hiccups, singultus) 5/23 (21.7%) 5 0/2 (0%) 0
    Hypoxia 5/23 (21.7%) 5 1/2 (50%) 1
    Nasal cavity/paranasal sinus reactions 1/23 (4.3%) 1 0/2 (0%) 0
    Pleural effusion (non-malignant) 9/23 (39.1%) 9 1/2 (50%) 1
    Pneumonitis/pulmonary infiltrates 2/23 (8.7%) 2 1/2 (50%) 1
    Pulmonary/Upper Respiratory - Other (Specify, __) 0/23 (0%) 0 1/2 (50%) 1
    Voice changes/dysarthria 3/23 (13%) 3 0/2 (0%) 0
    Skin and subcutaneous tissue disorders
    Bruising (in absence of Grade 3 or 4 thrombocytopenia) 2/23 (8.7%) 2 0/2 (0%) 0
    Dermatology/Skin - Other (Specify, __) 1/23 (4.3%) 1 0/2 (0%) 0
    Dry skin 14/23 (60.9%) 14 1/2 (50%) 1
    Flushing 14/23 (60.9%) 14 2/2 (100%) 2
    Hair loss/alopecia (scalp or body) 6/23 (26.1%) 6 0/2 (0%) 0
    Hyperpigmentation 19/23 (82.6%) 19 2/2 (100%) 2
    Hypopigmentation 2/23 (8.7%) 2 0/2 (0%) 0
    Induration/fibrosis (skin and subcutaneous tissue) 0/23 (0%) 0 1/2 (50%) 1
    Injection site reaction/extravasation changes 8/23 (34.8%) 8 2/2 (100%) 2
    Pruritus/itching 8/23 (34.8%) 8 1/2 (50%) 1
    Rash/dermatitis associated with high-dose chemotherapy or BMT studies. 1/23 (4.3%) 1 0/2 (0%) 0
    Rash/desquamation 22/23 (95.7%) 22 2/2 (100%) 2
    Rash: dermatitis associated with radiation 6/23 (26.1%) 6 0/2 (0%) 0
    Rash: hand-foot skin reaction 11/23 (47.8%) 11 0/2 (0%) 0
    Ulceration 2/23 (8.7%) 2 1/2 (50%) 1
    Urticaria (hives, welts, wheals) 1/23 (4.3%) 1 0/2 (0%) 0
    Vascular disorders
    INR (International Normalized Ratio of prothrombin time) 1/23 (4.3%) 1 0/2 (0%) 0
    PTT (Partial Thromboplastin Time) 6/23 (26.1%) 6 2/2 (100%) 2
    Thrombotic microangiopathy 1/23 (4.3%) 1 0/2 (0%) 0
    Hemorrhage, GI 9/23 (39.1%) 9 1/2 (50%) 1
    Hemorrhage, GU 8/23 (34.8%) 8 1/2 (50%) 1
    Hemorrhage, pulmonary/upper respiratory 9/23 (39.1%) 9 1/2 (50%) 1
    Petechiae/purpura (hemorrhage/bleeding into skin or mucosa) 4/23 (17.4%) 4 0/2 (0%) 0
    Thrombosis/embolism (vascular access-related) 4/23 (17.4%) 4 0/2 (0%) 0
    Thrombosis/thrombus/embolism 1/23 (4.3%) 1 0/2 (0%) 0

    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 Dr. Anthony Stein
    Organization City of Hope Medical Center
    Phone 626-359-8111
    Email
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT00540995
    Other Study ID Numbers:
    • 05013
    • NCI-2010-00354
    • CDR0000567452
    First Posted:
    Oct 8, 2007
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022