Melphalan and Radiation Therapy Followed By Lenalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Stage I, Stage II, or Stage III Multiple Myeloma
Sponsor
City of Hope Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT00112827
Collaborator
(none)
54
1
1
171.5
0.3
Study Details
Study Description
Brief Summary
RATIONALE: Melphalan, a chemotherapeutic agent, has been found to be an effective treatment choice for destroying myeloma cells, especially when given at high (bone marrow ablative) doses. Total marrow irradiation (TMI)/ablative dose radiation therapy is another modality capable of destroying myeloma cells. Autologous peripheral blood/stem cell transplant (ASCT) given after either melphalan or following TMI (aimed at the bone marrow containing areas of the skeleton, the site of origin of myeloma cells) will shorten the duration/alleviate the severity of both melphalan and marrow irradiation-associated side effects. Lenalidomide, an effective agent on its own right for the treatment of myeloma, has been shown to further enhance the beneficial effects of autologous stem cell transplants when given as maintenance therapy.
PURPOSE: This previously phase I trial established the maximum tolerated dose of TMI at 1600 cGy. The phase II part of this study is ongoing and is studying the effects of high-dose melphalan and ASCT, followed by TMI and a second ASCT, with subsequent maintenance lenalidomide. The study is conducted in patients with stages I-III myeloma, with specific emphasis on assessing complete and very good partial response rate conversions, progression-free and overall survival, and safety/feasibility of delivering the planned treatment regimen.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To assess the feasibility and toxicities of tandem cycle ablative therapy consisting first of high-dose melphalan and then escalating doses of fractionated total marrow irradiation (TMI) using helical tomotherapy in patients with advanced multiple myeloma.
-
To establish the maximum tolerated dose of TMI using helical tomotherapy. III. To assess response rate, progression free and over-all survival following treatment with tandem cycle ablative therapy consisting first of high-dose melphalan and then escalating doses of TMI using helical tomotherapy with Dexamethasone/Thalidomide maintenance therapy in patients with advanced multiple myeloma.
-
To assess the feasibility of adding decadron and thalidomide as maintenance following the second cycle of high-dose therapy.
SECONDARY OBJECTIVES:
-
To perform cytogenetic, gene rearrangement, and fluorescence in situ hybridization (FISH) studies on baseline and post-treatment bone marrow and blood specimens and correlate the presence/persistence of these features with treatment outcome.
-
To bank/develop cell lines developed for future investigations of tumor biology, and for potential assessment of efficacy of novel therapeutic agents.
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
PRIMING AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Patients also receive filgrastim IV or subcutaneously daily beginning 24 hours after the administration of cyclophosphamide and continuing until apheresis is complete. Patients undergo apheresis until an adequate number of peripheral blood stem cells are collected.
ABLATIVE THERAPY:
Course 1: Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1. Patients then undergo autologous PBSC transplantation on day 0 and receive filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts recover.
Course 2: Beginning 6-18 weeks later, patients undergo TMI once or twice daily on days -4 to -1. Patients then undergo autologous peripheral blood stem cell transplant and receive filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts recover.
MAINTENANCE THERAPY: Beginning within 6-8 weeks of day 0 of course 2 (TMI), patients receive oral lenalidomide daily. Courses repeat every 28 days for approximately 3 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days, every 6 months for 1 year, and then annually for at least 2 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
54 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial
Actual Study Start Date
:
Nov 1, 2004
Actual Primary Completion Date
:
Feb 15, 2019
Actual Study Completion Date
:
Feb 15, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I See Detailed Description |
Radiation: total marrow irradiation
Undergo irradiation
Drug: melphalan
Given IV
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
Biological: filgrastim
Given IV
Other Names:
Genetic: fluorescence in situ hybridization
Correlative studies
Other Names:
Genetic: cytogenetic analysis
Correlative studies
Drug: cyclophosphamide
Given IV
Other Names:
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Undergo transplantation
Drug: lenalidomide
Given orally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) [8 weeks from start of treatment, up to 2 years]
The highest dose tested (Total Marrow Irradiation) in which there is no treatment related mortality and none or only one patient experienced dose limited toxicity (DLT) attributable to the study drug(s), when at least six were fully treated at that dose and fully followed for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the treatment or there was a treatment related death. At least 6 patients will be treated at the MTD.
- Number of Subjects With Response [Evaluated after each course until completion of treatment.]
Response defined as complete response or very good partial response. Complete response defined as the absence of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval. Thus all evidence of serum and urinary M-components must disappear on electrophoresis as well as by immunofixation studies. The follow-up bone marrow may not contain more than 5% plasma cells on aspiration or core biopsy and no evidence of increasing anemia. Skeletal X-rays must either show recalcification or no change in osteolytic lesions. Resolution of soft tissue plasmocytomas. Very good partial response defined as reduction of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval by greater than or equal to 90%.
- Overall Survival [From date of treatment until the date of death from any cause, assessed up to 14 years]
Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Criteria
-
Patients with multiple myeloma (stages I-III) will be eligible if they are either in response, or have stable disease
-
Patients with smoldering myeloma are eligible if there is evidence of progressive disease requiring therapy (>= 25% increase in M protein levels or Bence Jones excretion; Hgb =< 10.5 g/dl; frequent infections; hypercalcemia; rise in serum creatinine above normal on two separate occasion)
-
Patients with non-quantifiable monoclonal proteins are eligible provided they meet other criteria for multiple myeloma, or smoldering myeloma, and they have evaluable or measurable disease by other (radiographic) means
-
Unlimited prior chemotherapy regimens allowed
-
KPS >= 70%
-
Patients with Waldenstrom's macroglobulinemia are not eligible
-
Less than 18 months since diagnosis
-
No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by apheresis
-
All patients must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
-
Adequate hepatic function as demonstrated by bilirubin, =< 1.5 mg/dl, and SGOT and SGPT < 2.5 x upper limits of normal
-
Adequate renal function as demonstrated by: creatinine of measured or calculated creatinine clearance of > 50 cc/min
-
Absolute neutrophil count of > 1000/ul, platelet count of > 100,000/ul
-
Cardiac ejection fraction >= 50% by MUGA scan and/or by echocardiogram
-
Adequate pulmonary function as demonstrated by FEV1 > 60% and DLCO > 50% of predicted lower limit
-
Hepatitis B antigen, Hepatitis C RNA and HIV antibody tests negative
-
No other medical, or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen
-
Females of reproductive age not using adequate birth control measures/ or who are pregnant are not eligible
-
History of other malignancies within the last 3 years, as long as patients have remained in complete remission for at least 2 years, except for non-melanoma skin cancer and in situ carcinoma of the cervix
-
Patients should have finished their prior chemotherapy at least 14 days prior to cyclophosphamide priming, and should have received their last dose of thalidomide, dexamethasone, or bisphosphonate > 10 days prior to cyclophosphamide priming
-
Pre-treatment tests must have been performed within 6 weeks prior to initiation of cyclophosphamide; A CBC, platelet count and comprehensive chemistry panel should be performed within 1 week prior to initiating cyclophosphamide priming
-
Known hypersensitivity to Filgrastim or to E. coli derived proteins is an exclusion
-
Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session, is an exclusion
-
Previous radiation therapy to more than 20% of bone marrow containing areas, or to any area exceeding 2000 cGy, is an exclusion
-
Patients must be fully aware of the teratogenic potential of thalidomide and agree to fully comply with the mandated guidelines regarding contraception as stated in the informed consent and the patient warning document attached to the consent form
-
Women of childbearing potential must have a negative pregnancy test performed within 24 hours prior to beginning thalidomide, except for woman who have been postmenopausal for at least 2 years, or underwent hysterectomy
-
Use of effective means of contraceptive should be started at least 2 weeks prior to initiating thalidomide
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Medical Center | Duarte | California | United States | 91010 |
Sponsors and Collaborators
- City of Hope Medical Center
Investigators
- Principal Investigator: George Somlo, City of Hope Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00112827
Other Study ID Numbers:
- COH 04064
- NCI-2009-01601
- CDR0000428410
First Posted:
Jun 3, 2005
Last Update Posted:
Mar 1, 2021
Last Verified:
Nov 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) |
|---|---|---|---|---|---|
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally |
| Period Title: Overall Study | |||||
| STARTED | 3 | 4 | 4 | 36 | 7 |
| COMPLETED | 3 | 4 | 4 | 36 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | Total of all reporting groups |
| Overall Participants | 3 | 4 | 4 | 36 | 7 | 54 |
| Age (years) [Median (Full Range) ] | ||||||
| Median (Full Range) [years] |
49
|
56
|
54
|
54
|
54
|
54
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
1
33.3%
|
2
50%
|
3
75%
|
13
36.1%
|
4
57.1%
|
23
42.6%
|
| Male |
2
66.7%
|
2
50%
|
1
25%
|
23
63.9%
|
3
42.9%
|
31
57.4%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| African American |
0
0%
|
0
0%
|
0
0%
|
6
16.7%
|
2
28.6%
|
8
14.8%
|
| Caucasian |
3
100%
|
2
50%
|
4
100%
|
22
61.1%
|
4
57.1%
|
35
64.8%
|
| Hispanic |
0
0%
|
1
25%
|
0
0%
|
5
13.9%
|
1
14.3%
|
7
13%
|
| Asian |
0
0%
|
1
25%
|
0
0%
|
2
5.6%
|
0
0%
|
3
5.6%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
1
2.8%
|
0
0%
|
1
1.9%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
4
100%
|
4
100%
|
36
100%
|
7
100%
|
54
100%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | The highest dose tested (Total Marrow Irradiation) in which there is no treatment related mortality and none or only one patient experienced dose limited toxicity (DLT) attributable to the study drug(s), when at least six were fully treated at that dose and fully followed for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the treatment or there was a treatment related death. At least 6 patients will be treated at the MTD. |
| Time Frame | 8 weeks from start of treatment, up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients enrolled in the dose-finding portion of the study. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally |
| Measure Participants | 24 |
| Number [cGy] |
1600
|
| Title | Number of Subjects With Response |
|---|---|
| Description | Response defined as complete response or very good partial response. Complete response defined as the absence of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval. Thus all evidence of serum and urinary M-components must disappear on electrophoresis as well as by immunofixation studies. The follow-up bone marrow may not contain more than 5% plasma cells on aspiration or core biopsy and no evidence of increasing anemia. Skeletal X-rays must either show recalcification or no change in osteolytic lesions. Resolution of soft tissue plasmocytomas. Very good partial response defined as reduction of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval by greater than or equal to 90%. |
| Time Frame | Evaluated after each course until completion of treatment. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) |
|---|---|---|---|---|---|
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally |
| Measure Participants | 3 | 4 | 4 | 36 | 7 |
| Count of Participants [Participants] |
3
100%
|
3
75%
|
2
50%
|
20
55.6%
|
4
57.1%
|
| Title | Overall Survival |
|---|---|
| Description | Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause. |
| Time Frame | From date of treatment until the date of death from any cause, assessed up to 14 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall survival was calculated for aggregated arms, due to small number of patients in most treatment arms. |
| Arm/Group Title | Treatment Arm |
|---|---|
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally |
| Measure Participants | 54 |
| Median (95% Confidence Interval) [months] |
95.8
|
Adverse Events
| Time Frame | Adverse events occurred over a period of 14 years and 3 months. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment. | |||||||||
| Arm/Group Title | Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | |||||
| Arm/Group Description | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | See Detailed Description total marrow irradiation: Undergo irradiation escalating according to the following schedule 1000cGy, 1200cGy, 1400cGy, 1600cGy, 1800cGy melphalan: Given IV peripheral blood stem cell transplantation: Undergo transplantation filgrastim: Given IV fluorescence in situ hybridization: Correlative studies cytogenetic analysis: Correlative studies cyclophosphamide: Given IV autologous-autologous tandem hematopoietic stem cell transplantation: Undergo transplantation lenalidomide: Given orally | |||||
All Cause Mortality |
||||||||||
| Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 3/4 (75%) | 4/4 (100%) | 20/36 (55.6%) | 4/7 (57.1%) | |||||
Serious Adverse Events |
||||||||||
| Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/4 (0%) | 0/4 (0%) | 6/36 (16.7%) | 3/7 (42.9%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| General disorders | ||||||||||
| Fatigue | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Fever | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||
| Colitis, infectious (e.g., Clostridium difficile) | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Sepsis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Hypophosphatemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Syncope | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Renal failure | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Pneumonitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Pain of skin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Rash desquamating | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||
| Hypotension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 3/4 (75%) | 33/36 (91.7%) | 7/7 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Febrile neutropenia | 1/3 (33.3%) | 2 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 11/36 (30.6%) | 11 | 1/7 (14.3%) | 1 |
| Hemoglobin decreased | 3/3 (100%) | 7 | 4/4 (100%) | 10 | 3/4 (75%) | 6 | 32/36 (88.9%) | 85 | 7/7 (100%) | 28 |
| Lymphatic disorder | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Arrhythmia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Atrial fibrillation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 1/7 (14.3%) | 1 |
| Cardiac disorder | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Conduction disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Left ventricular failure | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Mobitz type I | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Palpitations | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 5/36 (13.9%) | 5 | 1/7 (14.3%) | 1 |
| Pericardial effusion | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Pericarditis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Sinus bradycardia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Sinus tachycardia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Supraventricular tachycardia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Wolff-Parkinson-White syndrome | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 2 |
| Ear and labyrinth disorders | ||||||||||
| External ear pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Tinnitus | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Endocrine disorders | ||||||||||
| Adrenal insufficiency | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Hypothyroidism | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Eye disorders | ||||||||||
| Dry eye syndrome | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Flashing vision | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Vision blurred | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal distension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 5/36 (13.9%) | 6 | 1/7 (14.3%) | 2 |
| Abdominal pain | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 10/36 (27.8%) | 12 | 5/7 (71.4%) | 5 |
| Anal hemorrhage | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Anal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Constipation | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 3/4 (75%) | 5 | 18/36 (50%) | 26 | 5/7 (71.4%) | 6 |
| Diarrhea | 2/3 (66.7%) | 3 | 4/4 (100%) | 6 | 2/4 (50%) | 3 | 30/36 (83.3%) | 39 | 6/7 (85.7%) | 12 |
| Dry mouth | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 6/36 (16.7%) | 6 | 0/7 (0%) | 0 |
| Dyspepsia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 12/36 (33.3%) | 15 | 2/7 (28.6%) | 3 |
| Dysphagia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Ear, nose and throat examination abnormal | 2/3 (66.7%) | 2 | 2/4 (50%) | 2 | 2/4 (50%) | 2 | 11/36 (30.6%) | 14 | 0/7 (0%) | 0 |
| Esophageal mucositis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 3 | 1/7 (14.3%) | 1 |
| Esophageal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Esophagitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Flatulence | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 1/7 (14.3%) | 1 |
| Gastric mucositis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Gastritis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 5 | 2/7 (28.6%) | 3 |
| Gingival pain | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Hemorrhoids | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Mucositis oral | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 1/4 (25%) | 2 | 7/36 (19.4%) | 9 | 4/7 (57.1%) | 6 |
| Nausea | 3/3 (100%) | 6 | 4/4 (100%) | 7 | 3/4 (75%) | 6 | 29/36 (80.6%) | 50 | 7/7 (100%) | 15 |
| Oesophagoscopy abnormal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 3 | 0/7 (0%) | 0 |
| Oral pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Rectal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 6/36 (16.7%) | 6 | 0/7 (0%) | 0 |
| Retroperitoneal hemorrhage | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Stomach pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 4/36 (11.1%) | 5 | 0/7 (0%) | 0 |
| Vomiting | 3/3 (100%) | 5 | 3/4 (75%) | 5 | 2/4 (50%) | 3 | 23/36 (63.9%) | 32 | 6/7 (85.7%) | 9 |
| General disorders | ||||||||||
| Chest pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 2/7 (28.6%) | 2 |
| Chills | 1/3 (33.3%) | 1 | 2/4 (50%) | 2 | 1/4 (25%) | 2 | 7/36 (19.4%) | 7 | 2/7 (28.6%) | 2 |
| Disease progression | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 4/36 (11.1%) | 4 | 0/7 (0%) | 0 |
| Edema limbs | 2/3 (66.7%) | 5 | 2/4 (50%) | 2 | 1/4 (25%) | 1 | 10/36 (27.8%) | 12 | 4/7 (57.1%) | 6 |
| Facial pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Fatigue | 3/3 (100%) | 8 | 1/4 (25%) | 1 | 3/4 (75%) | 5 | 26/36 (72.2%) | 48 | 6/7 (85.7%) | 10 |
| Fever | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 9/36 (25%) | 9 | 1/7 (14.3%) | 1 |
| General symptom | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 6/36 (16.7%) | 7 | 0/7 (0%) | 0 |
| Ill-defined disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Injection site reaction | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Localized edema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pain | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 7/36 (19.4%) | 12 | 5/7 (71.4%) | 5 |
| Visceral edema | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Immune system disorders | ||||||||||
| Immune system disorder | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||
| Abdominal infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Anal infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Bronchitis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Catheter related infection | 2/3 (66.7%) | 2 | 2/4 (50%) | 4 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Colitis, infectious (e.g., Clostridium difficile) | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Conjunctivitis infective | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Gingival infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Infectious colitis | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Lip infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 1/7 (14.3%) | 1 |
| Opportunistic infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/36 (2.8%) | 3 | 0/7 (0%) | 0 |
| Peripheral nerve infection | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pneumonia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Sepsis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 10/36 (27.8%) | 10 | 1/7 (14.3%) | 1 |
| Skin infection | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Upper respiratory infection | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Urinary tract infection | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Wound dehiscence | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Investigations | ||||||||||
| Activated partial thromboplastin time prolonged | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Alanine aminotransferase increased | 2/3 (66.7%) | 3 | 4/4 (100%) | 6 | 2/4 (50%) | 5 | 19/36 (52.8%) | 29 | 7/7 (100%) | 13 |
| Alkaline phosphatase increased | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 7/36 (19.4%) | 8 | 3/7 (42.9%) | 3 |
| Aspartate aminotransferase increased | 3/3 (100%) | 4 | 3/4 (75%) | 4 | 3/4 (75%) | 6 | 17/36 (47.2%) | 27 | 6/7 (85.7%) | 11 |
| Bilirubin increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Blood gonadotrophin abnormal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Creatinine increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 5/36 (13.9%) | 8 | 2/7 (28.6%) | 2 |
| Electrocardiogram QTc interval prolonged | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Hypercholesterolemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| INR increased | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Laboratory test abnormal | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Leukocyte count decreased | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 30/36 (83.3%) | 63 | 4/7 (57.1%) | 11 |
| Leukopenia | 3/3 (100%) | 6 | 4/4 (100%) | 13 | 3/4 (75%) | 6 | 3/36 (8.3%) | 13 | 3/7 (42.9%) | 37 |
| Lymphocyte count decreased | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 19/36 (52.8%) | 31 | 2/7 (28.6%) | 5 |
| Lymphopenia | 3/3 (100%) | 6 | 4/4 (100%) | 11 | 3/4 (75%) | 6 | 3/36 (8.3%) | 9 | 3/7 (42.9%) | 23 |
| Neutrophil count decreased | 3/3 (100%) | 6 | 3/4 (75%) | 9 | 3/4 (75%) | 5 | 28/36 (77.8%) | 57 | 7/7 (100%) | 27 |
| Platelet count decreased | 3/3 (100%) | 6 | 4/4 (100%) | 10 | 3/4 (75%) | 6 | 32/36 (88.9%) | 70 | 7/7 (100%) | 43 |
| Serum cholesterol increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 7/36 (19.4%) | 8 | 1/7 (14.3%) | 1 |
| Weight gain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 8/36 (22.2%) | 10 | 3/7 (42.9%) | 3 |
| Weight loss | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 10/36 (27.8%) | 13 | 1/7 (14.3%) | 2 |
| Metabolism and nutrition disorders | ||||||||||
| Alkalosis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Anorexia | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 21/36 (58.3%) | 32 | 7/7 (100%) | 11 |
| Blood bicarbonate decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 5/36 (13.9%) | 5 | 3/7 (42.9%) | 7 |
| Blood glucose increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 22/36 (61.1%) | 31 | 2/7 (28.6%) | 4 |
| Blood uric acid increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 5 | 0/7 (0%) | 0 |
| Dehydration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 3 | 2/7 (28.6%) | 3 |
| Hypercalcemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 1/7 (14.3%) | 1 |
| Hyperglycemia | 2/3 (66.7%) | 4 | 3/4 (75%) | 4 | 2/4 (50%) | 2 | 3/36 (8.3%) | 3 | 3/7 (42.9%) | 6 |
| Hyperkalemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Hypoalbuminemia | 3/3 (100%) | 5 | 4/4 (100%) | 10 | 3/4 (75%) | 5 | 3/36 (8.3%) | 8 | 3/7 (42.9%) | 11 |
| Hypocalcemia | 3/3 (100%) | 6 | 4/4 (100%) | 8 | 3/4 (75%) | 6 | 3/36 (8.3%) | 6 | 3/7 (42.9%) | 12 |
| Hypoglycemia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 4 | 0/7 (0%) | 0 |
| Hypokalemia | 1/3 (33.3%) | 2 | 3/4 (75%) | 4 | 1/4 (25%) | 2 | 3/36 (8.3%) | 5 | 3/7 (42.9%) | 8 |
| Hypomagnesemia | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 3/4 (75%) | 4 | 1/36 (2.8%) | 2 | 1/7 (14.3%) | 2 |
| Hyponatremia | 0/3 (0%) | 0 | 2/4 (50%) | 4 | 2/4 (50%) | 2 | 3/36 (8.3%) | 5 | 3/7 (42.9%) | 6 |
| Hypophosphatemia | 2/3 (66.7%) | 2 | 4/4 (100%) | 8 | 2/4 (50%) | 3 | 3/36 (8.3%) | 7 | 3/7 (42.9%) | 8 |
| Obesity | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Serum albumin decreased | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 29/36 (80.6%) | 53 | 4/7 (57.1%) | 10 |
| Serum calcium decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 28/36 (77.8%) | 50 | 4/7 (57.1%) | 7 |
| Serum calcium increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 7/36 (19.4%) | 8 | 2/7 (28.6%) | 3 |
| Serum glucose decreased | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 11/36 (30.6%) | 12 | 0/7 (0%) | 0 |
| Serum magnesium decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 11/36 (30.6%) | 15 | 3/7 (42.9%) | 4 |
| Serum magnesium increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 2/7 (28.6%) | 2 |
| Serum phosphate decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 21/36 (58.3%) | 32 | 4/7 (57.1%) | 5 |
| Serum potassium decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 18/36 (50%) | 28 | 4/7 (57.1%) | 8 |
| Serum potassium increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Serum sodium decreased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 21/36 (58.3%) | 34 | 4/7 (57.1%) | 7 |
| Serum sodium increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Serum triglycerides increased | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 4 | 1/7 (14.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Back pain | 3/3 (100%) | 7 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 18/36 (50%) | 29 | 4/7 (57.1%) | 5 |
| Bone pain | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 10/36 (27.8%) | 13 | 2/7 (28.6%) | 2 |
| Chest wall pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 1/7 (14.3%) | 1 |
| Joint effusion | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Joint pain | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 4/36 (11.1%) | 4 | 1/7 (14.3%) | 1 |
| Muscle weakness | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Muscle weakness lower limb | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Myalgia | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 7/36 (19.4%) | 9 | 2/7 (28.6%) | 2 |
| Myositis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Neck pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 3/36 (8.3%) | 4 | 0/7 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 14/36 (38.9%) | 19 | 2/7 (28.6%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumor pain | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Depressed level of consciousness | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 1/7 (14.3%) | 1 |
| Dizziness | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 6/36 (16.7%) | 8 | 5/7 (71.4%) | 5 |
| Headache | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 1/4 (25%) | 2 | 18/36 (50%) | 23 | 3/7 (42.9%) | 4 |
| Memory impairment | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 1/7 (14.3%) | 1 |
| Neuralgia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Neurological disorder NOS | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 2/7 (28.6%) | 3 |
| Oculomotor nerve disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Peripheral motor neuropathy | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Peripheral sensory neuropathy | 2/3 (66.7%) | 4 | 0/4 (0%) | 0 | 3/4 (75%) | 6 | 21/36 (58.3%) | 35 | 3/7 (42.9%) | 7 |
| Sinus pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Speech disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Syncope | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Taste alteration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 4/36 (11.1%) | 4 | 0/7 (0%) | 0 |
| Tremor | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 2 |
| Psychiatric disorders | ||||||||||
| Agitation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Anxiety | 2/3 (66.7%) | 3 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 10/36 (27.8%) | 11 | 2/7 (28.6%) | 2 |
| Depression | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 3/36 (8.3%) | 4 | 1/7 (14.3%) | 1 |
| Insomnia | 3/3 (100%) | 4 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 11/36 (30.6%) | 16 | 4/7 (57.1%) | 5 |
| Renal and urinary disorders | ||||||||||
| Bladder pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Cystitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Hemorrhage urinary tract | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Protein urine positive | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 5/36 (13.9%) | 7 | 1/7 (14.3%) | 1 |
| Renal failure | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Urethral pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Urinary frequency | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Urinary retention | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 1/7 (14.3%) | 1 |
| Urogenital disorder | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Gynecomastia | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Pelvic pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 6/36 (16.7%) | 7 | 0/7 (0%) | 0 |
| Perineal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Vaginal hemorrhage | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Vaginal inflammation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Allergic rhinitis | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Apnea | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Atelectasis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Bronchospasm | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Cough | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 11/36 (30.6%) | 15 | 4/7 (57.1%) | 4 |
| Dyspnea | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 4 | 0/7 (0%) | 0 |
| Hemorrhage nasal | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 2/4 (50%) | 2 | 1/36 (2.8%) | 2 | 1/7 (14.3%) | 1 |
| Hiccough | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Hypoxia | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Laryngeal mucositis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Laryngeal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Nasal congestion | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Pharyngolaryngeal pain | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 4 | 0/7 (0%) | 0 |
| Pleural effusion | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Pneumonitis | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 2 | 0/7 (0%) | 0 |
| Respiratory disorder | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/36 (0%) | 0 | 1/7 (14.3%) | 4 |
| Voice alteration | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 4/36 (11.1%) | 5 | 1/7 (14.3%) | 1 |
| Decubitus ulcer | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Dry skin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/36 (8.3%) | 3 | 0/7 (0%) | 0 |
| Erythema multiforme | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Nail disorder | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Pain of skin | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Petechiae | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pruritus | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 5/36 (13.9%) | 5 | 0/7 (0%) | 0 |
| Rash acneiform | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Rash desquamating | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 22/36 (61.1%) | 29 | 6/7 (85.7%) | 9 |
| Skin disorder | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 6/36 (16.7%) | 7 | 1/7 (14.3%) | 2 |
| Skin hyperpigmentation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 5/36 (13.9%) | 5 | 0/7 (0%) | 0 |
| Skin hypopigmentation | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Sweating | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/36 (5.6%) | 2 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||
| Flushing | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 5/36 (13.9%) | 6 | 1/7 (14.3%) | 2 |
| Hemorrhage | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Hot flashes | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 0/7 (0%) | 0 |
| Hypertension | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 9/36 (25%) | 12 | 1/7 (14.3%) | 1 |
| Hypotension | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 6/36 (16.7%) | 7 | 1/7 (14.3%) | 1 |
| Phlebitis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/36 (2.8%) | 1 | 0/7 (0%) | 0 |
| Thrombosis | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/36 (0%) | 0 | 1/7 (14.3%) | 1 |
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 | Paul Frankel, Ph.D. |
|---|---|
| Organization | City of Hope |
| Phone | 626-218-5265 |
| pfrankel@coh.org |
Responsible Party:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00112827
Other Study ID Numbers:
- COH 04064
- NCI-2009-01601
- CDR0000428410
First Posted:
Jun 3, 2005
Last Update Posted:
Mar 1, 2021
Last Verified:
Nov 1, 2019