Re-MATCH: Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
Study Details
Study Description
Brief Summary
Immunotherapy is a specific approach to treating cancer that has shown promise in adult patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study investigators will use the experience they have gained from these studies to try to improve the outcome for children affected by a recurrent brain tumor.
Approximately 35 patients with first recurrence of medulloblastoma (reMB)/supratentorial primitive neuroectodermal tumors (PNETs) will be treated with tumor-specific immune cells and dendritic cell vaccines to see what impact they have on the tumor.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Malignant brain tumors now represent the most frequent cause of cancer death in children. Despite aggressive and highly toxic multi-modality therapy including surgery, craniospinal radiation, and high-dose chemotherapy coupled with peripheral blood stem cell transplantation, almost half the children diagnosed with the most common malignant brain tumors, medulloblastoma (MB) and primitive neuroectodermal tumors (PNET), will still die from recurrent disease. Furthermore, survivors are often left with severe and lifelong treatment-associated cognitive and motor deficits. The development of more effective and tumor-specific therapies that will not add further toxicity to existing treatments is paramount in improving clinical outcomes for children affected by MB/PNETs. Immunotherapy targeting tumor-specific antigens expressed within brain tumors is a modality potentially capable of meeting this clear and urgent need.
Despite considerable advancements and promising clinical results observed in immunotherapy trials directed against adult malignant brain tumors, efforts in the immunologic treatment of pediatric brain tumors have been limited to relatively few notable studies. This is due, at least in part, to the often limited viable tumor tissue available for tumor cell-based vaccine preparations, and the lack of identification of consistently expressed tumor-specific antigens within these cancers.
The use of total tumor RNA (TTRNA)-loaded dendritic cells (DCs) was pioneered at Duke University, as a novel platform for inducing potent immunologic responses against the variety of uncharacterized and patient-specific antigens present within malignant tumor cells. Duke demonstrated that sufficient RNA for clinical vaccine preparations can be amplified with high fidelity using existing molecular technologies from as few as 500 isolated pediatric and adult brain tumor cells, thus allowing vaccine preparation from surgical biopsies and even microdissected archival tumor specimens.
Immunotherapy administered during recovery from chemotherapy may have tremendous advantages, as adoptive cellular therapy following lymphodepletive conditioning regimens has emerged as the most effective treatment strategy for advanced and refractory melanoma. Our hypothesis is that DC + ex vivo expanded Autologous Lymphocyte Transfer (xALT) therapy targeting recurrent MB/PNETs during recovery from myeloablative chemotherapy will be safe and will prolong survival in children and young adults with recurrent MB/PNETs.
In this study, the investigators will treat patients with first recurrence reMB/PNETs after completion of definitive radiation therapy with autologous tumor-specific T cell immunotherapy (TTRNA-xALT) plus TTRNA-loaded dendritic cell vaccine.
Following surgical resection, biopsy, or cytology examination with confirmatory pathologic diagnosis, patients will be enrolled into Group A (high-dose chemotherapy or HDC) or Group B (non-myeloablative or NMA salvage chemotherapy) based on eligibility for HDC. Patients with localized relapse and have not failed HDC+ peripheral blood stem cell transplant (PBSCT) previously will be enrolled into Group A. Patients with disseminated disease, have previously failed HDC+PBSCT, or are otherwise considered poor candidates for HDC based on overall health status, but otherwise meet eligibility criteria, will be enrolled into Group B. All patients will receive DC + xALT therapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. |
Biological: TTRNA-xALT
TTRNA-xALT 3 x 10^7/kg by intravenous injection once.
Biological: TTRNA-DCs
TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
|
| Experimental: Group B NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. |
Biological: TTRNA-xALT
TTRNA-xALT 3 x 10^7/kg by intravenous injection once.
Biological: TTRNA-DCs
TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
|
Outcome Measures
Primary Outcome Measures
- 12 Month Progression-free Survival (PFS-12) [up to 12 months]
PFS is defined as time interval from date of first DC vaccine to date of progression (death is also treated as progression) or censoring, whichever happens first.
Secondary Outcome Measures
- Objective Radiographic Response Rate [best overall radiographic response through duration on study (up to 60 months)]
Radiographic response will be assessed as a percentage change in tumor size from pre-treatment (baseline) MRI scans of the brain and spine obtained with and without contrast. Evaluation will be based on the NCI-endorsed, World Health Organization RECIST criteria and using a modified version of the MacDonald criteria (complete response, partial response, stable disease, progressive disease or not assessible).
- Correlate Magnitude and Persistence of Anti-tumor Humoral or Cellular Immunity With Clinical Outcome [baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)]
Peripheral blood will be used to compare pre-therapy lymphocyte function to defined intervals after each immunization. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.
- Evaluate Changes in Cytokine Profile and Toll-Like Receptor Activation Status [baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)]
We will measure serum cytokines pre and post therapy. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.
- Characterize Immunologic Phenotype of Lymphocyte Subsets and NK Cells [baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)]
We will conduct flow cytometry from patient samples. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks.
- Determine of Overall Survival Rate [up to 60 months]
Kaplan-Meier estimator will be used to describe length of overall survival from initiation of vaccine #1 for both Groups A and B.
Eligibility Criteria
Criteria
Inclusion Criteria:
Screening:
-
Age ≤ 30 years of age.
-
Suspected first recurrence/progression of MB/PNET since completion of definitive focal +/- craniospinal irradiation. Disease progression prior to receiving definitive focal +/- craniospinal irradiation will not disqualify patients from enrollment if they have subsequently failed definitive radiotherapy and are at first recurrence/progression at time of enrollment. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression.
Re-MATCH Protocol:
-
Patients must have histologically confirmed recurrent MB/PNET that is a first relapse/progression after completion of definitive radiotherapy +/- craniospinal irradiation. Patients with a first relapse/progression who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (ie. Gorlin's syndrome or NF1 mutation) are eligible for enrollment.
-
Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
-
Karnofsky Performance Status of ≥ 50% or Lansky Performance Score of ≥ 50.
-
Absolute Neutrophil Count (ANC) ≥ 1000/µl (unsupported).
-
Platelets ≥ 100,000/µl (unsupported).
-
Hemoglobin > 8 g/dL (may be supported).
-
Serum creatinine ≤ upper limit of institutional normal
-
Bilirubin ≤ 1.5 times upper limit of normal for age.
-
Serum Glutamic Oxaloacetic Transaminase (ALT) ≤ 3 times institutional upper limit of normal for age.
-
Serum Glutamic Oxaloacetic Transaminase (AST) ≤ 3 times institutional upper limit of normal for age.
-
Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
-
Patient or patient guardian consent to peripheral blood stem cell (PBSC) and/or bone marrow harvest following registration if PBSC or bone marrow (CD34 count of at least 2x10^6/kg) has not been previously stored and available for use.
-
Signed informed consent according to institutional guidelines must be obtained prior to registration.
Exclusion Criteria:
-
Pregnant or need to breast feed during the study period.
-
Active infection requiring treatment or an unexplained febrile (> 101.5F) illness.
-
Known immunosuppressive disease, human immunodeficiency virus infection, or carriers of Hepatitis B or Hepatitis C virus.
-
Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
-
Patients receiving concomitant immunosuppressive agents for medical condition.
-
Patients who need definitive radiotherapy for treatment of recurrent MB/PNET. Focal boost radiotherapy may be delivered prior to immunotherapy if required for local control.
-
Patients receiving any other concurrent anticancer or investigational drug therapy.
-
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
-
Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 3 | University of Florida | Gainesville | Florida | United States | 32610 |
Sponsors and Collaborators
- University of Florida
- United States Department of Defense
Investigators
- Principal Investigator: Duane Mitchell, MD, PhD, University of Florida
Study Documents (Full-Text)
More Information
Publications
None provided.- IRB201500502
- W81XWH-10-1-0089
- CDMRP-PRO93877
- OCR13166
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Thirty-six patients were assessed for eligibility in the Phase II trial. Ten subjects were excluded; seven did not meet eligibility and three declined participation prior to allocation to intervention arm. |
| Arm/Group Title | Group A | Group B |
|---|---|---|
| Arm/Group Description | High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. |
| Period Title: Overall Study | ||
| STARTED | 7 | 19 |
| COMPLETED | 7 | 15 |
| NOT COMPLETED | 0 | 4 |
Baseline Characteristics
| Arm/Group Title | Group A | Group B | Total |
|---|---|---|---|
| Arm/Group Description | High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | Total of all reporting groups |
| Overall Participants | 7 | 15 | 22 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
15
|
10
|
12.5
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
28.6%
|
5
33.3%
|
7
31.8%
|
| Male |
5
71.4%
|
10
66.7%
|
15
68.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
3
20%
|
3
13.6%
|
| Not Hispanic or Latino |
7
100%
|
12
80%
|
19
86.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
6.7%
|
1
4.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
4
26.7%
|
4
18.2%
|
| White |
7
100%
|
9
60%
|
16
72.7%
|
| More than one race |
0
0%
|
1
6.7%
|
1
4.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
7
100%
|
15
100%
|
22
100%
|
Outcome Measures
| Title | 12 Month Progression-free Survival (PFS-12) |
|---|---|
| Description | PFS is defined as time interval from date of first DC vaccine to date of progression (death is also treated as progression) or censoring, whichever happens first. |
| Time Frame | up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group A | Group B |
|---|---|---|
| Arm/Group Description | High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. |
| Measure Participants | 7 | 15 |
| Median (95% Confidence Interval) [Days] |
215
|
69
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group A |
|---|---|---|
| Comments | Based on published literature, PFS-12 for patients with recurrent disease after initiating treatment with HDC + PBSCT or standard salvage therapy was 33% (95% confidence interval of 10%, 59%). The study was designed to differentiate between a PFS-12 rate of 33% (null hypothesis) and 55% (alternative hypothesis). If 35 patients enrolled, this assessment has 90% power assuming a type I error rate of 0.10. We assume that PFS of historical controls follows exponential distribution. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.927 |
| Comments | This is the p-value comparing Group A with historical control. | |
| Method | Log Rank | |
| Comments | One sample log rank. | |
| Method of Estimation | Estimation Parameter | comparing two curves |
| Estimated Value | 0.286 | |
| Confidence Interval |
(2-Sided) 90% 0.107 to 0.764 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group B |
|---|---|---|
| Comments | Based on published literature, PFS-12 for patients with recurrent disease after initiating treatment with HDC + PBSCT or standard salvage therapy was 33% (95% confidence interval of 10%, 59%). The study was designed to differentiate between a PFS-12 rate of 33% (null hypothesis) and 55% (alternative hypothesis). If 35 patients enrolled, this assessment has 90% power assuming a type I error rate of 0.10. We assume that PFS of historical controls follows exponential distribution. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | This is the p-value comparing Group B with historical control. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | compare two curves |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group A, Group B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | This is the p-value comparing Groups A and B combined with historical control. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Comparing two curves |
| Estimated Value | 0.091 | |
| Confidence Interval |
(2-Sided) 90% 0.03 to 0.276 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Radiographic Response Rate |
|---|---|
| Description | Radiographic response will be assessed as a percentage change in tumor size from pre-treatment (baseline) MRI scans of the brain and spine obtained with and without contrast. Evaluation will be based on the NCI-endorsed, World Health Organization RECIST criteria and using a modified version of the MacDonald criteria (complete response, partial response, stable disease, progressive disease or not assessible). |
| Time Frame | best overall radiographic response through duration on study (up to 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Correlate Magnitude and Persistence of Anti-tumor Humoral or Cellular Immunity With Clinical Outcome |
|---|---|
| Description | Peripheral blood will be used to compare pre-therapy lymphocyte function to defined intervals after each immunization. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks. |
| Time Frame | baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Evaluate Changes in Cytokine Profile and Toll-Like Receptor Activation Status |
|---|---|
| Description | We will measure serum cytokines pre and post therapy. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks. |
| Time Frame | baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Characterize Immunologic Phenotype of Lymphocyte Subsets and NK Cells |
|---|---|
| Description | We will conduct flow cytometry from patient samples. Blood will be obtained for immunologic monitoring prior to non-mobilized leukapheresis, prior to immunotherapy, 1 day post Vaccine #1, 4 (+/- 1) days post Vaccine #1, weekly post Vaccine #1 for six weeks. |
| Time Frame | baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Determine of Overall Survival Rate |
|---|---|
| Description | Kaplan-Meier estimator will be used to describe length of overall survival from initiation of vaccine #1 for both Groups A and B. |
| Time Frame | up to 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | There are two AE periods. The first begins at initiation of non-mobilized leukapheresis and ends 24 hrs after completion of the procedure. The second starts with initiation of consolidation or NMA chemotherapy and continues until 100 days after either the infusion of PBSCs or completion of chemotherapy for subjects not receiving PBSCs. AEs are not collected from the end of the leukapheresis period until the start of consolidation/NMA chemotherapy when subjects received salvage chemotherapy. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | An "AE" will be defined as any adverse change from the subject's pre-treatment baseline condition, including any clinical or laboratory test abnormality that occurs during the course of research after treatment has started. A summary of recorded AEs will be kept which will categorize the event by organ system, relationship to treatment, its grade of severity, and resolution. | |||
| Arm/Group Title | Group A | Group B | ||
| Arm/Group Description | High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. TTRNA-xALT: TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs: TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses. | ||
All Cause Mortality |
||||
| Group A | Group B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/7 (85.7%) | 17/19 (89.5%) | ||
Serious Adverse Events |
||||
| Group A | Group B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/7 (57.1%) | 5/19 (26.3%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile Neutropenia | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Cardiac disorders | ||||
| Cardiac Arrest | 0/7 (0%) | 0 | 1/19 (5.3%) | 1 |
| Tachycardia | 1/7 (14.3%) | 1 | 0/19 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Hearing impaired | 2/7 (28.6%) | 2 | 0/19 (0%) | 0 |
| General disorders | ||||
| Pain | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Infections and infestations | ||||
| Colitis, Infectious | 0/7 (0%) | 0 | 1/19 (5.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Acidosis | 0/7 (0%) | 0 | 1/19 (5.3%) | 1 |
| Hyperbilirubinemia | 1/7 (14.3%) | 1 | 0/19 (0%) | 0 |
| Nervous system disorders | ||||
| Hydrocephalus | 0/7 (0%) | 0 | 1/19 (5.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Hypoxia | 1/7 (14.3%) | 1 | 0/19 (0%) | 0 |
| Respiratory Arrest | 0/7 (0%) | 0 | 1/19 (5.3%) | 1 |
| Vascular disorders | ||||
| Hypotension | 2/7 (28.6%) | 2 | 0/19 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Group A | Group B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 19/19 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 7/7 (100%) | 19 | 10/19 (52.6%) | 25 |
| Decreased platelet count | 4/7 (57.1%) | 5 | 3/19 (15.8%) | 3 |
| Leukopenia | 3/7 (42.9%) | 5 | 3/19 (15.8%) | 5 |
| Cardiac disorders | ||||
| Chest pain | 2/7 (28.6%) | 3 | 0/19 (0%) | 0 |
| Eye disorders | ||||
| Blurred vision | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal Pain | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Diarrhea | 5/7 (71.4%) | 5 | 2/19 (10.5%) | 4 |
| Dysphagia | 1/7 (14.3%) | 2 | 1/19 (5.3%) | 1 |
| Vomiting | 4/7 (57.1%) | 5 | 2/19 (10.5%) | 2 |
| Mucositis oral | 6/7 (85.7%) | 6 | 1/19 (5.3%) | 1 |
| Nausea | 5/7 (71.4%) | 8 | 4/19 (21.1%) | 6 |
| General disorders | ||||
| Fever | 4/7 (57.1%) | 6 | 2/19 (10.5%) | 4 |
| Infections and infestations | ||||
| Enterocolitis | 1/7 (14.3%) | 1 | 1/19 (5.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Pain - access site | 2/7 (28.6%) | 2 | 0/19 (0%) | 0 |
| Investigations | ||||
| Increased ALT | 1/7 (14.3%) | 4 | 1/19 (5.3%) | 2 |
| White blood cell decreased | 5/7 (71.4%) | 12 | 9/19 (47.4%) | 23 |
| Lymphocyte count decreased | 6/7 (85.7%) | 16 | 14/19 (73.7%) | 28 |
| neutrophil count decreased | 5/7 (71.4%) | 13 | 12/19 (63.2%) | 21 |
| Platelet count decreased | 3/7 (42.9%) | 22 | 5/19 (26.3%) | 9 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 5/7 (71.4%) | 7 | 2/19 (10.5%) | 3 |
| hypermagnesemia | 1/7 (14.3%) | 1 | 1/19 (5.3%) | 1 |
| hypocalcemia | 1/7 (14.3%) | 1 | 2/19 (10.5%) | 4 |
| hypokalemia | 2/7 (28.6%) | 2 | 1/19 (5.3%) | 1 |
| hypomagnesemia | 1/7 (14.3%) | 3 | 1/19 (5.3%) | 3 |
| hypophosphatemia | 4/7 (57.1%) | 5 | 1/19 (5.3%) | 5 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/7 (14.3%) | 1 | 1/19 (5.3%) | 1 |
| Muscle weakness right-sided | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Nervous system disorders | ||||
| Ataxia | 0/7 (0%) | 0 | 2/19 (10.5%) | 2 |
| Confusion | 2/7 (28.6%) | 2 | 0/19 (0%) | 0 |
| Headache | 1/7 (14.3%) | 2 | 1/19 (5.3%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 2/7 (28.6%) | 3 | 2/19 (10.5%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| epistaxis | 3/7 (42.9%) | 5 | 0/19 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 3/7 (42.9%) | 3 | 0/19 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension | 1/7 (14.3%) | 1 | 2/19 (10.5%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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 | Kristine Wynne |
|---|---|
| Organization | University of Florida |
| Phone | 352-273-9727 |
| kristine.wynne@neurosurgery.ufl.edu |
- IRB201500502
- W81XWH-10-1-0089
- CDMRP-PRO93877
- OCR13166