Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01027000
Collaborator
National Cancer Institute (NCI) (NIH), Genentech, Inc. (Industry), Biologics, Inc. (Industry)
68
Enrollment
25
Locations
1
Arm
2.7
Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

OBJECTIVES:

Primary

  • To determine if this treatment can improve 2-year current progression-free survival (PFS) in the early disease cohort compared to historical controls. Specifically, we plan to study whether we can achieve 2-year PFS ≥ 70% and to exclude 2 year PFS ≤ 50%

Secondary

  • To determine whether in the advanced disease cohort we can achieve 2-year current PFS ≥ 50% and to exclude 2-year PFS ≤ 30%

  • To assess objective response rate.

  • To assess the incidence of grade 2-4 and 3-4 acute graft-vs-host disease (GVHD).

  • To assess the incidence of extensive chronic GVHD.

  • To assess the incidence of treatment-related mortality at 100 days and 1 year

  • To assess overall survival

  • To assess donor chimerism for CD3+ cells at 1 and 2 years after transplantation

  • To investigate the presence of donor antigen-specific T-cell clones before and after withdrawal of immune suppression.

  • To compare the relapse profiles of patients with T-cell responses against CLL to those whose CLL cells are not reactive

  • To prospectively examine the impact of high-risk genomic features and immune-based single nucleotide polymorphisms on response, toxicity, and 2-year PFS to reduced intensity allogeneic stem cell transplant

OUTLINE: This is a multicenter study.

  • Preparative regimen: Patients receive 1 of 2 preparative regimens at the discretion of the participating institution.

  • Preparative regimen 1: Patients receive rituximab IV on days -7, -1, 7, and 14 and fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -5 to -2. .

  • Preparative regimen 2: Patients receive rituximab IV on days -7, -1, 7, and 14, fludarabine phosphate IV over 30 minutes on days -5 to -2, and cyclophosphamide IV over 1-2 hours on days -5 to -3. Patients with matched unrelated donors also receive anti-thymocyte globulin IV over 4-6 hours on days -6 to -4.

  • Graft-vs-host disease (GVHD) prophylaxis: Patients who receive preparative regimen 1 may receive either GVHD prophylaxis regimen 1 or 2; patients who receive preparative regimen 2 may only receive GVHD prophylaxis regimen 2.

  • GVHD prophylaxis regimen 1: Patients receive tacrolimus either orally or IV and oral sirolimus beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6.

  • GVHD prophylaxis regimen 2: Patients receive tacrolimus either orally or IV beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

  • Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

  • Maintenance therapy: Patients receive rituximab IV at 3, 6, 9, and 12 months after transplantation.

Peripheral blood and bone marrow aspirate samples may be collected periodically for correlative laboratory studies.

Patients are followed up periodically for a maximum of 5 years from study entry.

Study Design

Study Type:
Interventional
Actual Enrollment :
68 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)
Study Start Date :
Feb 1, 2010
Actual Primary Completion Date :
Jan 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (Combination of chemotherapy and transplant)

See detailed description

Biological: rituximab

Drug: busulfan

Drug: cyclophosphamide

Drug: fludarabine phosphate

Drug: methotrexate

Drug: sirolimus

Drug: tacrolimus

Procedure: allogeneic stem cell transplant

Outcome Measures

Primary Outcome Measures

  1. 2-year Progression-free Survival in Early Disease Participants [2 years post-registration]

    Percentage of participants who were alive and progression free at 2 years for participants with early disease stage. The 2 year progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method. A progression is defined as one of the following events: >= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be >= 2 cm); appearance of new palpable lymph nodes. >= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present. > 50% increase in peripheral blood lymphocytes with an absolute increase > 5000/μL. Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with >= 56% prolymphocytes).

Secondary Outcome Measures

  1. Response [5 years post-registration]

  2. Acute Graft-vs-host Disease (GVHD) [5 years post-registration]

  3. Chronic GVHD [5 years post-registration]

  4. Treatment-related Mortality [6 months post-transplant]

  5. Overall Survival [5 years post-registration]

  6. Chimerism for CD3 [5 years post-registration]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 69 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Patient Eligibility:
  1. Diagnosis of B-cell chronic lymphocytic leukemia or B-cell small lymphocytic lymphoma.

Diagnosis should be according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria

  1. Early Disease Cohort - Patients in the early disease cohort must include one or more of the following:
  • FISH showing deletion 17p in ≥ 20% of cells (either at diagnosis or any time prior to study entry) either alone or in combination with other cytogenetic abnormalities

  • FISH showing del 11q in ≥ 20% of cells (either at diagnosis or any time prior to study entry) either alone or in combination with other cytogenetic abnormalities, unless the patient has achieved a complete remission by IWCLL 2008 which includes CT scan, bone marrow morphology and flow cytometry

  • Failure to achieve a partial response with initial chemotherapy, but with lack of progression. These patients may receive a second therapy to improve their response prior to transplant.

  • Patients who, at the time of first progression, have a 17p deletion by FISH in ≥ 20% of cells, either alone or in combination with other cytogenetic abnormalities.

The duration of the first progression is not specified.

  • In addition, patients in the early disease cohort must have all of the following:

  • Received at least 2 cycles of induction therapy. It is expected that most patients will receive at least 4 months of therapy prior to enrollment, but this is not required. Suggested regimens include but are not limited to the following: fludarabine plus rituximab, fludarabine, cyclophosphamide plus rituximab, pentostatin, cyclophosphamide plus rituximab, bendumustine plus rituximab, or alemtuzumab alone or in combination with other agents. Patients may receive no more than 2 different regimens prior to proceeding to transplantation.

  • Nodes ≤ 5 cm

  1. Advanced Disease Cohort - Patients in the advanced disease cohort must include one or more of the following:
  • FISH showing deletion 17p in ≥ 20% of cells (regardless of interval from initial therapy) either alone or in combination with other cytogenetic abnormalities

  • First progression < 24 months after completing therapy. This includes progression on initial therapy.

  • Second or subsequent progression

  • In addition, patients in the advanced disease cohort must have all of the following:

  • Stable disease or better by the Revised IWCLL 2008 NCI Criteria to their most recent chemotherapy

  • Nodes ≤ 5 cm

  1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

  2. Age Requirement - Patients must be between ≥ 18 and < 70 years of age

  3. Cytotoxic Chemotherapy or Alemtuzamab - There must be at least 4 weeks after day 1 of the last cycle of cytotoxic chemotherapy, or alemtuzamab.

  4. Human Immunodeficiency Virus (HIV) Status - Patients must have no HIV infection.

Allogeneic transplantation in the HIV patient population is not well-defined and there are likely to be requirements for concomitant anti-HIV therapy and anti-GVHD therapy that would create potentially dangerous pharmacokinetic interactions among the different agents that could constrain therapeutic options for controlling both HIV and GVHD.

  1. Hepatitis B and C - Patients must have no Hepatitis B sAg, anti-HBc or HCV.

  2. Diffusion capacity of carbon monoxide DLCO must be ≥ 40% predicted

  3. Left ventricular ejection fraction (LVEF) by Echocardiogram (ECHO) or Multiple gated acquisition (MUGA) must be ≥ 30%

  4. Diabetes or Serious Infection - Patients must have no uncontrolled diabetes mellitus or active uncontrolled serious infections

  5. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks. Women of childbearing potential should have a negative pregnancy test prior to study entry.

Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).

  1. Richter's Transformation - Patients must have no history of Richter's transformation.

  2. Initial Required Laboratory Values:

  • Serum Creatinine < 2 mg/dL

  • Calculated Creatinine Clearance ≥ 40 mL/min

  • AST < 3 x ULN

  • Total Bilirubin < 2 mg/dL (except for Gilbert's syndrome)

Donor Eligibility:
  1. Donors may be either a 6/6 HLA-matched related donor by low-resolution typing at HLA A, B, DR.

  2. Donors may be an 8/8 HLA-matched unrelated donor at HLA A, B, C, DR. Unrelated donors will be analyzed by molecular typing at both HLA Class I and Class II (A, B, C, DR loci).

  3. Syngeneic donors are not eligible

  4. Donors must be healthy and must be an acceptable donor as per institutional standards for stem cell donation.

  5. There will be no donor age restriction.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1City of Hope Comprehensive Cancer CenterDuarteCaliforniaUnited States91010-3000
2Tunnell Cancer Center at Beebe Medical CenterLewesDelawareUnited States19958
3CCOP - Christiana Care Health ServicesNewarkDelawareUnited States19713
4Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlandoFloridaUnited States32803-1273
5H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampaFloridaUnited States33612-9497
6University of Chicago Cancer Research CenterChicagoIllinoisUnited States60637-1470
7Holden Comprehensive Cancer Center at University of IowaIowa CityIowaUnited States52242-1002
8Union Hospital of Cecil CountyElktonMarylandUnited States21921
9Massachusetts General HospitalBostonMassachusettsUnited States02114
10Dana-Farber/Brigham and Women's Cancer CenterBostonMassachusettsUnited States02115
11Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115
12Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSaint LouisMissouriUnited States63110
13UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmahaNebraskaUnited States68198-6805
14Cancer Institute of New Jersey at Cooper - VoorheesVoorheesNew JerseyUnited States08043
15Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263-0001
16Monter Cancer Center of the North Shore-LIJ Health SystemLake SuccessNew YorkUnited States11042
17CCOP - North Shore University HospitalManhassetNew YorkUnited States11030
18Don Monti Comprehensive Cancer Center at North Shore University HospitalManhassetNew YorkUnited States11030
19Long Island Jewish Medical CenterNew Hyde ParkNew YorkUnited States11040
20New York Weill Cornell Cancer Center at Cornell UniversityNew YorkNew YorkUnited States10021
21Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065
22Wake Forest University Comprehensive Cancer CenterWinston-SalemNorth CarolinaUnited States27157-1096
23Cleveland Clinic Taussig Cancer CenterClevelandOhioUnited States44195
24Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbusOhioUnited States43210-1240
25Oklahoma University Cancer InstituteOklahoma CityOklahomaUnited States73104

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)
  • Genentech, Inc.
  • Biologics, Inc.

Investigators

  • Study Chair: Edwin P. Alyea, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01027000
Other Study ID Numbers:
  • CALGB 100701
  • CDR0000660555
  • U10CA031946
  • NCI-2011-01995
First Posted:
Dec 7, 2009
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021

Study Results

Participant Flow

Recruitment DetailsBetween February 2010 and January 2014, 68 participants were recruited.
Pre-assignment Detail
Arm/Group TitleTreatment (Combination of Chemotherapy and Transplant)
Arm/Group DescriptionPreparative: Patients receive 1 of 2 preparative regimens (Reg) chosen by the treating institution Reg1: Rituximab (RTX) 500 mg/m^2 IV on days -7, -1, 7, and 14 & fludarabine phosphate (FP) 30 mg/m^2 IV & busulfan 0.8 mg/kg IV on days -5 to -2 Reg 2: RTX 500 mg/m^2 IV on days -7, -1, 7, and 14 & FP 30 mg/m^2 IV on days -5 to -2 & cyclophosphamide 1 g/m^2 IV on days -5 to -3 Graft-vs-host disease (GVHD) prophylaxis: Patients treated with preparative regimen 1 received either GVHD prophylaxis regimen 1 or 2; those given preparative regimen 2 received regimen 2 Reg 1: Tacrolimus PO or IV & oral sirolimus 12 mg on day -2 through day 60, followed by taper until day 180 & methotrexate (MTX) 5 mg/m^2 IV on days 1, 3, and 6. Reg 2: Tacrolimus PO or IV on day -2 through day 60, followed by taper until day 180 & MTX 5mg/m^2 IV on days 1, 3, 6, & 11 Transplantation: allogeneic peripheral blood transplant on day 0 Maintenance: RTX 500 mg/m^2 IV at 3, 6, 9, & 12 months post-transplant
Period Title: Overall Study
STARTED68
COMPLETED68
NOT COMPLETED0

Baseline Characteristics

Arm/Group TitleTreatment (Combination of Chemotherapy and Transplant)
Arm/Group DescriptionPreparative: Patients receive 1 of 2 preparative regimens (Reg) chosen by the treating institution Reg1: Rituximab (RTX) 500 mg/m^2 IV on days -7, -1, 7, and 14 & fludarabine phosphate (FP) 30 mg/m^2 IV & busulfan 0.8 mg/kg IV on days -5 to -2 Reg 2: RTX 500 mg/m^2 IV on days -7, -1, 7, and 14 & FP 30 mg/m^2 IV on days -5 to -2 & cyclophosphamide 1 g/m^2 IV on days -5 to -3 Graft-vs-host disease (GVHD) prophylaxis: Patients treated with preparative regimen 1 received either GVHD prophylaxis regimen 1 or 2; those given preparative regimen 2 received regimen 2 Reg 1: Tacrolimus PO or IV & oral sirolimus 12 mg on day -2 through day 60, followed by taper until day 180 & methotrexate (MTX) 5 mg/m^2 IV on days 1, 3, and 6. Reg 2: Tacrolimus PO or IV on day -2 through day 60, followed by taper until day 180 & MTX 5mg/m^2 IV on days 1, 3, 6, & 11 Transplantation: allogeneic peripheral blood transplant on day 0 Maintenance: RTX 500 mg/m^2 IV at 3, 6, 9, & 12 months post-transplant
Overall Participants68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
56
Sex: Female, Male (Count of Participants)
Female
22
32.4%
Male
46
67.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
2
2.9%
Not Hispanic or Latino
62
91.2%
Unknown or Not Reported
4
5.9%
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
1
1.5%
White
66
97.1%
More than one race
0
0%
Unknown or Not Reported
1
1.5%
Region of Enrollment (participants) [Number]
United States
68
100%
Disease stage (participants) [Number]
Early Disease
14
20.6%
Advanced Disease
50
73.5%
Not reported
4
5.9%

Outcome Measures

1. Primary Outcome
Title2-year Progression-free Survival in Early Disease Participants
DescriptionPercentage of participants who were alive and progression free at 2 years for participants with early disease stage. The 2 year progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method. A progression is defined as one of the following events: >= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be >= 2 cm); appearance of new palpable lymph nodes. >= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present. > 50% increase in peripheral blood lymphocytes with an absolute increase > 5000/μL. Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with >= 56% prolymphocytes).
Time Frame2 years post-registration

Outcome Measure Data

Analysis Population Description
Participants with early disease stage were analyzed. Two participants, who did not start protocol therapy, were excluded from this analysis.
Arm/Group TitleTreatment (Combination of Chemotherapy and Transplant)
Arm/Group DescriptionPreparative: Patients receive 1 of 2 preparative regimens (Reg) chosen by the treating institution Reg1: Rituximab (RTX) 500 mg/m^2 IV on days -7, -1, 7, and 14 & fludarabine phosphate (FP) 30 mg/m^2 IV & busulfan 0.8 mg/kg IV on days -5 to -2 Reg 2: RTX 500 mg/m^2 IV on days -7, -1, 7, and 14 & FP 30 mg/m^2 IV on days -5 to -2 & cyclophosphamide 1 g/m^2 IV on days -5 to -3 Graft-vs-host disease (GVHD) prophylaxis: Patients treated with preparative regimen 1 received either GVHD prophylaxis regimen 1 or 2; those given preparative regimen 2 received regimen 2 Reg 1: Tacrolimus PO or IV & oral sirolimus 12 mg on day -2 through day 60, followed by taper until day 180 & methotrexate (MTX) 5 mg/m^2 IV on days 1, 3, and 6. Reg 2: Tacrolimus PO or IV on day -2 through day 60, followed by taper until day 180 & MTX 5mg/m^2 IV on days 1, 3, 6, & 11 Transplantation: allogeneic peripheral blood transplant on day 0 Maintenance: RTX 500 mg/m^2 IV at 3, 6, 9, & 12 months post-transplant
Measure Participants12
Median (95% Confidence Interval) [percentage of participants]
79.5
116.9%
2. Secondary Outcome
TitleResponse
Description
Time Frame5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
3. Secondary Outcome
TitleAcute Graft-vs-host Disease (GVHD)
Description
Time Frame5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
4. Secondary Outcome
TitleChronic GVHD
Description
Time Frame5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
5. Secondary Outcome
TitleTreatment-related Mortality
Description
Time Frame6 months post-transplant

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
6. Secondary Outcome
TitleOverall Survival
Description
Time Frame5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
7. Secondary Outcome
TitleChimerism for CD3
Description
Time Frame5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time Frame
Adverse Event Reporting Description Adverse event data is available for 59 participants . The remaining 9 participants cancelled before beginning treatment or withdrew consent for follow-up.
Arm/Group TitleTreatment (Combination of Chemotherapy and Transplant)
Arm/Group DescriptionPreparative: Patients receive 1 of 2 preparative regimens (Reg) chosen by the treating institution Reg1: Rituximab (RTX) 500 mg/m^2 IV on days -7, -1, 7, and 14 & fludarabine phosphate (FP) 30 mg/m^2 IV & busulfan 0.8 mg/kg IV on days -5 to -2 Reg 2: RTX 500 mg/m^2 IV on days -7, -1, 7, and 14 & FP 30 mg/m^2 IV on days -5 to -2 & cyclophosphamide 1 g/m^2 IV on days -5 to -3 Graft-vs-host disease (GVHD) prophylaxis: Patients treated with preparative regimen 1 received either GVHD prophylaxis regimen 1 or 2; those given preparative regimen 2 received regimen 2 Reg 1: Tacrolimus PO or IV & oral sirolimus 12 mg on day -2 through day 60, followed by taper until day 180 & methotrexate (MTX) 5 mg/m^2 IV on days 1, 3, and 6. Reg 2: Tacrolimus PO or IV on day -2 through day 60, followed by taper until day 180 & MTX 5mg/m^2 IV on days 1, 3, 6, & 11 Transplantation: allogeneic peripheral blood transplant on day 0 Maintenance: RTX 500 mg/m^2 IV at 3, 6, 9, & 12 months post-transplant
All Cause Mortality
Treatment (Combination of Chemotherapy and Transplant)
Affected / at Risk (%)# Events
Total/ (NaN)
Serious Adverse Events
Treatment (Combination of Chemotherapy and Transplant)
Affected / at Risk (%)# Events
Total6/59 (10.2%)
Blood and lymphatic system disorders
Anemia5/59 (8.5%) 8
Ear and labyrinth disorders
Vertigo1/59 (1.7%) 3
Eye disorders
Corneal ulcer1/59 (1.7%) 1
Eye disorders - Other, specify1/59 (1.7%) 1
Keratitis1/59 (1.7%) 1
Gastrointestinal disorders
Diarrhea1/59 (1.7%) 1
Mucositis oral1/59 (1.7%) 1
Nausea1/59 (1.7%) 3
Vomiting1/59 (1.7%) 3
General disorders
Edema limbs1/59 (1.7%) 1
Fatigue3/59 (5.1%) 3
Infections and infestations
Infections and infestations - Other, specify1/59 (1.7%) 1
Lung infection2/59 (3.4%) 2
Sepsis1/59 (1.7%) 1
Skin infection1/59 (1.7%) 1
Urinary tract infection2/59 (3.4%) 2
Vaginal infection1/59 (1.7%) 1
Investigations
Alanine aminotransferase increased2/59 (3.4%) 2
Aspartate aminotransferase increased1/59 (1.7%) 1
Blood bilirubin increased2/59 (3.4%) 2
Cholesterol high1/59 (1.7%) 1
Creatinine increased4/59 (6.8%) 5
Investigations - Other, specify1/59 (1.7%) 1
Lymphocyte count decreased3/59 (5.1%) 5
Neutrophil count decreased4/59 (6.8%) 6
Platelet count decreased6/59 (10.2%) 7
White blood cell decreased3/59 (5.1%) 4
Metabolism and nutrition disorders
Anorexia1/59 (1.7%) 1
Glucose intolerance1/59 (1.7%) 2
Hyperglycemia5/59 (8.5%) 6
Hypertriglyceridemia1/59 (1.7%) 1
Hypoalbuminemia2/59 (3.4%) 2
Hypocalcemia2/59 (3.4%) 2
Hypokalemia1/59 (1.7%) 1
Hypomagnesemia1/59 (1.7%) 1
Hyponatremia1/59 (1.7%) 1
Nervous system disorders
Dizziness1/59 (1.7%) 3
Dysphasia1/59 (1.7%) 1
Edema cerebral1/59 (1.7%) 1
Intracranial hemorrhage2/59 (3.4%) 2
Nervous system disorders - Other, specify2/59 (3.4%) 4
Stroke1/59 (1.7%) 1
Tremor1/59 (1.7%) 1
Psychiatric disorders
Psychiatric disorders - Other, specify1/59 (1.7%) 1
Renal and urinary disorders
Chronic kidney disease1/59 (1.7%) 1
Reproductive system and breast disorders
Genital edema1/59 (1.7%) 1
Skin and subcutaneous tissue disorders
Pruritus1/59 (1.7%) 1
Rash maculo-papular4/59 (6.8%) 4
Vascular disorders
Hypertension3/59 (5.1%) 3
Hypotension2/59 (3.4%) 2
Thromboembolic event1/59 (1.7%) 1
Other (Not Including Serious) Adverse Events
Treatment (Combination of Chemotherapy and Transplant)
Affected / at Risk (%)# Events
Total58/59 (98.3%)
Blood and lymphatic system disorders
Anemia48/59 (81.4%) 161
Blood and lymphatic system disorders - Other, specify2/59 (3.4%) 4
Febrile neutropenia6/59 (10.2%) 7
Hemolysis1/59 (1.7%) 1
Leukocytosis5/59 (8.5%) 5
Cardiac disorders
Atrioventricular block first degree1/59 (1.7%) 1
Palpitations1/59 (1.7%) 1
Restrictive cardiomyopathy1/59 (1.7%) 1
Sinus bradycardia2/59 (3.4%) 2
Sinus tachycardia4/59 (6.8%) 5
Supraventricular tachycardia1/59 (1.7%) 1
Ear and labyrinth disorders
Ear pain1/59 (1.7%) 4
Tinnitus1/59 (1.7%) 1
Endocrine disorders
Cushingoid3/59 (5.1%) 4
Endocrine disorders - Other, specify1/59 (1.7%) 4
Eye disorders
Blurred vision3/59 (5.1%) 3
Cataract1/59 (1.7%) 1
Corneal ulcer1/59 (1.7%) 2
Dry eye6/59 (10.2%) 11
Eye disorders - Other, specify5/59 (8.5%) 7
Eye pain1/59 (1.7%) 1
Keratitis1/59 (1.7%) 1
Papilledema1/59 (1.7%) 1
Photophobia1/59 (1.7%) 1
Scleral disorder1/59 (1.7%) 1
Gastrointestinal disorders
Abdominal distension4/59 (6.8%) 7
Abdominal pain13/59 (22%) 21
Ascites2/59 (3.4%) 6
Colonic ulcer1/59 (1.7%) 1
Constipation11/59 (18.6%) 14
Diarrhea28/59 (47.5%) 54
Dry mouth6/59 (10.2%) 16
Dyspepsia3/59 (5.1%) 3
Dysphagia1/59 (1.7%) 1
Enterocolitis1/59 (1.7%) 1
Esophagitis1/59 (1.7%) 1
Gastritis3/59 (5.1%) 3
Gastrointestinal disorders - Other, specify4/59 (6.8%) 4
Gastrointestinal pain1/59 (1.7%) 3
Hemorrhoids2/59 (3.4%) 2
Ileus1/59 (1.7%) 1
Lip pain1/59 (1.7%) 1
Malabsorption1/59 (1.7%) 1
Mucositis oral9/59 (15.3%) 9
Nausea29/59 (49.2%) 64
Oral pain3/59 (5.1%) 4
Pancreatitis1/59 (1.7%) 1
Rectal pain2/59 (3.4%) 2
Stomach pain1/59 (1.7%) 1
Toothache1/59 (1.7%) 1
Vomiting17/59 (28.8%) 28
General disorders
Chills8/59 (13.6%) 11
Edema face5/59 (8.5%) 5
Edema limbs17/59 (28.8%) 42
Fatigue34/59 (57.6%) 105
Fever17/59 (28.8%) 22
Infusion related reaction2/59 (3.4%) 2
Injection site reaction1/59 (1.7%) 1
Irritability2/59 (3.4%) 2
Localized edema1/59 (1.7%) 1
Malaise3/59 (5.1%) 3
Neck edema1/59 (1.7%) 1
Non-cardiac chest pain2/59 (3.4%) 2
Pain4/59 (6.8%) 8
Hepatobiliary disorders
Cholecystitis2/59 (3.4%) 3
Hepatic failure1/59 (1.7%) 1
Hepatobiliary disorders - Other, specify5/59 (8.5%) 10
Immune system disorders
Allergic reaction2/59 (3.4%) 2
Infections and infestations
Abdominal infection1/59 (1.7%) 1
Bronchial infection1/59 (1.7%) 1
Catheter related infection2/59 (3.4%) 2
Eye infection1/59 (1.7%) 1
Hepatic infection1/59 (1.7%) 1
Infections and infestations - Other, specify9/59 (15.3%) 14
Joint infection1/59 (1.7%) 1
Lip infection1/59 (1.7%) 1
Lung infection8/59 (13.6%) 9
Meningitis1/59 (1.7%) 1
Mucosal infection2/59 (3.4%) 4
Rhinitis infective1/59 (1.7%) 1
Sepsis2/59 (3.4%) 2
Sinusitis2/59 (3.4%) 9
Skin infection1/59 (1.7%) 1
Upper respiratory infection9/59 (15.3%) 15
Urinary tract infection1/59 (1.7%) 1
Vaginal infection1/59 (1.7%) 1
Injury, poisoning and procedural complications
Bruising1/59 (1.7%) 3
Fall1/59 (1.7%) 1
Fracture2/59 (3.4%) 2
Hip fracture1/59 (1.7%) 1
Intraoperative renal injury1/59 (1.7%) 1
Investigations
Activated partial thromboplastin time prolonged7/59 (11.9%) 8
Alanine aminotransferase increased26/59 (44.1%) 65
Alkaline phosphatase increased17/59 (28.8%) 37
Aspartate aminotransferase increased25/59 (42.4%) 71
Blood bilirubin increased21/59 (35.6%) 44
Cholesterol high8/59 (13.6%) 12
Creatinine increased36/59 (61%) 70
INR increased1/59 (1.7%) 1
Investigations - Other, specify13/59 (22%) 51
Lymphocyte count decreased35/59 (59.3%) 97
Lymphocyte count increased7/59 (11.9%) 9
Neutrophil count decreased51/59 (86.4%) 137
Platelet count decreased52/59 (88.1%) 143
Weight gain1/59 (1.7%) 1
Weight loss7/59 (11.9%) 9
White blood cell decreased33/59 (55.9%) 80
Metabolism and nutrition disorders
Anorexia10/59 (16.9%) 14
Dehydration1/59 (1.7%) 1
Hypercalcemia1/59 (1.7%) 1
Hyperglycemia40/59 (67.8%) 153
Hyperkalemia14/59 (23.7%) 22
Hypermagnesemia4/59 (6.8%) 4
Hypernatremia7/59 (11.9%) 9
Hypertriglyceridemia14/59 (23.7%) 19
Hyperuricemia1/59 (1.7%) 1
Hypoalbuminemia19/59 (32.2%) 34
Hypocalcemia26/59 (44.1%) 50
Hypoglycemia4/59 (6.8%) 5
Hypokalemia13/59 (22%) 18
Hypomagnesemia25/59 (42.4%) 52
Hyponatremia18/59 (30.5%) 39
Hypophosphatemia12/59 (20.3%) 22
Metabolism and nutrition disorders - Other, specify4/59 (6.8%) 9
Obesity9/59 (15.3%) 27
Musculoskeletal and connective tissue disorders
Abdominal soft tissue necrosis1/59 (1.7%) 1
Arthralgia8/59 (13.6%) 12
Arthritis4/59 (6.8%) 7
Back pain15/59 (25.4%) 21
Bone pain2/59 (3.4%) 2
Chest wall pain1/59 (1.7%) 1
Flank pain4/59 (6.8%) 4
Generalized muscle weakness4/59 (6.8%) 6
Musculoskeletal and connective tissue disorder - Other, specify4/59 (6.8%) 6
Myalgia7/59 (11.9%) 9
Neck pain3/59 (5.1%) 5
Osteoporosis1/59 (1.7%) 1
Pain in extremity5/59 (8.5%) 5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify1/59 (1.7%) 3
Nervous system disorders
Ataxia1/59 (1.7%) 1
Dizziness7/59 (11.9%) 11
Dysesthesia1/59 (1.7%) 1
Dysgeusia3/59 (5.1%) 4
Headache23/59 (39%) 31
Lethargy1/59 (1.7%) 1
Nervous system disorders - Other, specify1/59 (1.7%) 1
Neuralgia2/59 (3.4%) 3
Paresthesia2/59 (3.4%) 3
Peripheral motor neuropathy3/59 (5.1%) 3
Peripheral sensory neuropathy7/59 (11.9%) 14
Sinus pain3/59 (5.1%) 5
Stroke1/59 (1.7%) 2
Syncope1/59 (1.7%) 1
Transient ischemic attacks1/59 (1.7%) 1
Tremor14/59 (23.7%) 25
Psychiatric disorders
Agitation1/59 (1.7%) 4
Anxiety7/59 (11.9%) 16
Confusion1/59 (1.7%) 1
Delirium1/59 (1.7%) 1
Depression7/59 (11.9%) 12
Hallucinations1/59 (1.7%) 1
Insomnia8/59 (13.6%) 9
Libido decreased2/59 (3.4%) 2
Psychiatric disorders - Other, specify1/59 (1.7%) 1
Renal and urinary disorders
Acute kidney injury2/59 (3.4%) 2
Cystitis noninfective2/59 (3.4%) 2
Hematuria2/59 (3.4%) 3
Renal and urinary disorders - Other, specify2/59 (3.4%) 2
Urinary frequency3/59 (5.1%) 6
Urinary urgency1/59 (1.7%) 1
Urine discoloration1/59 (1.7%) 2
Reproductive system and breast disorders
Erectile dysfunction1/59 (1.7%) 1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis2/59 (3.4%) 9
Apnea2/59 (3.4%) 3
Aspiration2/59 (3.4%) 3
Atelectasis1/59 (1.7%) 2
Bronchopleural fistula1/59 (1.7%) 1
Cough22/59 (37.3%) 44
Dyspnea15/59 (25.4%) 28
Epistaxis4/59 (6.8%) 5
Hoarseness1/59 (1.7%) 1
Hypoxia4/59 (6.8%) 5
Nasal congestion7/59 (11.9%) 8
Pharyngolaryngeal pain2/59 (3.4%) 2
Pleural effusion3/59 (5.1%) 3
Pleuritic pain2/59 (3.4%) 3
Pneumonitis6/59 (10.2%) 8
Postnasal drip2/59 (3.4%) 3
Productive cough3/59 (5.1%) 3
Respiratory failure2/59 (3.4%) 2
Respiratory, thoracic and mediastinal disorders - Other, specify5/59 (8.5%) 10
Sinus disorder1/59 (1.7%) 1
Sleep apnea2/59 (3.4%) 3
Sore throat7/59 (11.9%) 7
Wheezing1/59 (1.7%) 1
Skin and subcutaneous tissue disorders
Alopecia1/59 (1.7%) 2
Dry skin5/59 (8.5%) 12
Erythema multiforme1/59 (1.7%) 1
Pain of skin1/59 (1.7%) 1
Periorbital edema2/59 (3.4%) 2
Pruritus11/59 (18.6%) 20
Rash maculo-papular33/59 (55.9%) 68
Skin and subcutaneous tissue disorders - Other, specify10/59 (16.9%) 12
Skin hyperpigmentation4/59 (6.8%) 5
Skin hypopigmentation1/59 (1.7%) 1
Skin ulceration2/59 (3.4%) 2
Urticaria1/59 (1.7%) 1
Surgical and medical procedures
Surgical and medical procedures - Other, specify1/59 (1.7%) 2
Vascular disorders
Flushing2/59 (3.4%) 2
Hot flashes2/59 (3.4%) 4
Hypertension25/59 (42.4%) 76
Hypotension5/59 (8.5%) 5
Superficial thrombophlebitis1/59 (1.7%) 1
Thromboembolic event4/59 (6.8%) 4

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/TitleEdwin P. Alyea, MD
OrganizationDana Farber Cancer Institute
Phone
Emailedwin_alyea@dfci.harvard.edu
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01027000
Other Study ID Numbers:
  • CALGB 100701
  • CDR0000660555
  • U10CA031946
  • NCI-2011-01995
First Posted:
Dec 7, 2009
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021