Busulfan, Etoposide, and Intensity-Modulated Radiation Therapy Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Myeloid Cancer
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:
- 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
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:
Drug: etoposide
Given IV
Other Names:
Radiation: intensity-modulated radiation therapy
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
Other Names:
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:
Procedure: peripheral blood stem cell transplantation
Stem cell transplantation occurs on Day 0 after High Dose Therapy
Other Names:
Radiation: tomotherapy
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
Other Names:
|
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:
Drug: etoposide
Given IV
Other Names:
Radiation: intensity-modulated radiation therapy
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
Other Names:
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:
Procedure: peripheral blood stem cell transplantation
Stem cell transplantation occurs on Day 0 after High Dose Therapy
Other Names:
Radiation: tomotherapy
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
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.- 05013
- NCI-2010-00354
- CDR0000567452
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
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
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 |
- 05013
- NCI-2010-00354
- CDR0000567452