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Bortezomib and Vorinostat in Younger Patients With Refractory or Relapsed MLL Rearranged Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02419755
Recruitment Status : Terminated (Accrual goals were no longer feasible based on restrictions imposed by the DSMB.)
First Posted : April 17, 2015
Results First Posted : February 1, 2018
Last Update Posted : March 7, 2018
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Mixed Lineage Acute Leukemia
Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Interventions Drug: Bortezomib
Drug: Vorinostat
Drug: Mitoxantrone
Drug: Cytarabine
Drug: Methotrexate
Drug: Hydrocortisone
Drug: Peg-L-Asparaginase
Drug: Erwinia L-Asparaginase
Drug: Dexamethasone
Drug: Mercaptopurine
Drug: Doxorubicin
Enrollment 12
Recruitment Details Twelve participants were enrolled at St. Jude Children's Research Hospital between April 2015 and October 2016.
Pre-assignment Details  
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description. Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Period Title: Overall Study
Started 6 6
Completed 3 2
Not Completed 3 4
Reason Not Completed
Death             1             3
Relapse             0             1
Ineligible             1             0
Withdrawal by Subject             1             0
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM Total
Hide Arm/Group Description Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description. Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description. Total of all reporting groups
Overall Number of Baseline Participants 4 6 10
Hide Baseline Analysis Population Description
Although only 3 Stratum 1 and 4 Stratum 2 participants completed the trial, there were 4 Stratum 1 participants and 6 Stratum 2 participants evaluable for the outcome measures and adverse events. Basic Characteristics are provided for the evaluable participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 6 participants 10 participants
3.39836  (1.22932) 4.58224  (5.33903) 4.10869  (4.08824)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 6 participants 10 participants
Female
0
   0.0%
3
  50.0%
3
  30.0%
Male
4
 100.0%
3
  50.0%
7
  70.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 6 participants 10 participants
Not Otherwise Specified, Spanish, Hispanic, Latino
0
   0.0%
2
  33.3%
2
  20.0%
Non Spanish speaking, Non Hispanic
4
 100.0%
3
  50.0%
7
  70.0%
South or Central American
0
   0.0%
1
  16.7%
1
  10.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 6 participants 10 participants
Asian and White
0
   0.0%
1
  16.7%
1
  10.0%
White
4
 100.0%
5
  83.3%
9
  90.0%
1.Primary Outcome
Title Overall Response Rate in All Participants
Hide Description

For the purpose of the statistical analysis of the primary objective, response is assessed at the end of first treatment block at maximum tolerated dose of vorinostat (i.e., Induction Ia or Ib for myeloid and Induction for lymphoid and mixed lineage). Any eligible patient who starts first treatment block is considered evaluable. Response of CR, CRi, PR, or PRi is considered a success; otherwise a failure, which will include the cases of No-response, as well as off- treatment or off-study before response can be assessed, except cases found ineligible after enrollment. A patient found ineligible after enrollment will be taken off study and replaced by enrolling an additional MLLr patient.

The rate (probability) of response will be estimated by the sample proportion of patients who responded (CR, CRi, PR, PRi) to Induction, along with the 99% confidence interval and lower confidence bound. Three interim analyses will be performed to monitor the possible lack of efficacy.

Time Frame End of first treatment block (up to 2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The determination of overall response rate is contingent on the determination of the maximum tolerated dose. The study was terminated before the maximum tolerated dose was determined. Therefore, response rate cannot be calculated.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Number of Participants With 3 Year Event Free Survival (EFS)
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. In addition to death for any reason, no-response (i.e., other than CR, CRi, PR or PRi), off-treatment or off-study (except for the reason of being found ineligible), disease progression, relapse, and second malignancies will be considered as failures. The time to EFS will be set to 0 for patients who fail to respond.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Three years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Number of Participants With 5- Year Event Free Survival
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. In addition to death for any reason, no-response (i.e., other than CR, CRi, PR or PRi), off-treatment or off-study (except for the reason of being found ineligible), disease progression, relapse, and second malignancies will be considered as failures. The time to EFS will be set to 0 for patients who fail to respond.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Five years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Participant With 10-year Event Free Survival
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. In addition to death for any reason, no-response (i.e., other than CR, CRi, PR or PRi), off-treatment or off-study (except for the reason of being found ineligible), disease progression, relapse, and second malignancies will be considered as failures. The time to EFS will be set to 0 for patients who fail to respond.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Ten years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants With 3-year Overall Survival (OS)
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. Death for any reason is considered as a failure.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Three years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Number of Participants With 5-year Overall Survival
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. Death for any reason is considered as a failure.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Five years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants With 10-year Overall Survival
Hide Description

All eligible patients who started the treatment will be included in this analysis. Patients later found ineligible will be replaced and excluded from the estimation. Death for any reason is considered as a failure.

Kaplan-Meier estimates of the OS and EFS functions will be computed, along with estimates of standard errors by the method of Peto. Three-year OS and EFS rates, as well as longer term survival rates (5 year and 10 year) will be estimated with 95% confidence intervals.

Time Frame Ten years after the last enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started the treatment at the vorinostat maximum tolerated dose will be included in this analysis. The study was terminated before the maximum tolerated dose was determined.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Number of Relevant Toxicities Related to Therapy
Hide Description

Events were graded using CTCAE v. 4.0. All toxicities will be monitored until the completion of therapy (up to 500 days) for patients that do not go on to bone marrow transplant. If a patient goes on to receive a bone marrow transplant, at that point, they will no longer be monitored for toxicity, as any further toxicities may be secondary to the transplant and not the study regimen.

This outcome reports those toxicities that are that were possibly, probably or definitely related to therapy. Participants were separately monitored for frequency of grade 5 events, grade 4 sepsis, grade 4 hemorrhage, and grade 4 hepatic toxicity across all patients in the stratum. Grade 4 and 5 events that are clearly and incontrovertibly due to extraneous causes or disease progression will be excluded. Higher grade events are considered more severe than lower grade.

Time Frame From on-therapy date up to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Although only 3 Stratum 1 and 4 Stratum 2 participants completed the trial, there were 4 Stratum 1 participants and 6 Stratum 2 participants evaluable for this outcome measures.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 4 6
Measure Type: Number
Unit of Measure: events
Grade 5: death 1 3
Grade 4: sepsis 0 2
Grade 4: hemorrhage 0 1
Grade 4: hepatic toxicity 0 0
9.Other Pre-specified Outcome
Title Frequency of Identified Genomic Lesions
Hide Description Frequencies of the identified lesions will be described by counts and proportions. An established method (Pounds et al., 2013) will be applied to identify genes and pathways frequently hit by the genomic lesions.
Time Frame Once at enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
The investigator is unable to identify frequency of genomic lesions. To obtain useful information, a much larger sample size is needed. Genomic sequencing is cost-prohibitive to be performed on this small sample size where there are too few samples to obtain any useful information.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Other Pre-specified Outcome
Title Minimal Residual Disease (MRD)
Hide Description

MRD will be monitored until the completion of therapy (up to 500 days) for patients that do not go on to bone marrow transplant. If a patient goes on to receive a bone marrow transplant, at that point, they will no longer be monitored for minimal residual disease.

Concordance and associations of the MRD levels across three modalities (flow cytometry, PCR, and deep sequencing) as continuous measurements will be assessed by Pearson’s and Spearman’s correlations and Kendall’s tau; MRD levels categorized into ordinal values will be analyzed by contingency tables with or without ordered margins.

Time Frame Various time points until completion of therapy (up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was either not collected or is incomplete for each of the 10 participants, and therefore cannot be analyzed.
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description:
Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description.
Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were recorded from a participant's on-study date until they were taken off study, up to 8 months. Although only 3 Stratum 1 and 4 Stratum 2 participants completed the trial, there were 4 Stratum 1 participants and 6 Stratum 2 participants evaluable for adverse events.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Hide Arm/Group Description Participants receive cytarabine, bortezomib, vorinostat, methotrexate, hydrocortisone, mitoxantrone as described in the Detailed Study Description. Participants in Stratum 2 [Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLM)] receive mitoxantrone, PEG-L-Asparaginase (or Erwinia L-asparaginase), dexamethasone, bortezomib, vorinostat, cytarabine, methotrexate, hydrocortisone, mercaptopurine, and doxorubicin as described in the Detailed Study Description.
All-Cause Mortality
Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)      6/6 (100.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/4 (25.00%)      2/6 (33.33%)    
Cardiac disorders     
Heart failure * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Infections and infestations     
Lung infection * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Hypoxia * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Bronchopulmonary hemorrhage * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Pneumothorax * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Stratum 1: Myeloid Malignancies Stratum 2: ALL and MLM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders     
Anemia * 1  3/4 (75.00%)  33 3/6 (50.00%)  23
Febrile neutropenia * 1  3/4 (75.00%)  4 1/6 (16.67%)  1
Cardiac disorders     
General disorders * 1  1/4 (25.00%)  2 0/6 (0.00%)  0
Pericardial effusion * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Sinus bradycardia * 1  1/4 (25.00%)  2 1/6 (16.67%)  1
Gastrointestinal disorders     
Abdominal pain * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Colitis * 1  1/4 (25.00%)  1 2/6 (33.33%)  3
Diarrhea * 1  1/4 (25.00%)  1 2/6 (33.33%)  4
Gastric hemorrhage * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Gastric ulcer * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Gastroesophageal reflux disease * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Ileus * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Typhlitis * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Upper gastrointestinal hemorrhage * 1  0/4 (0.00%)  0 2/6 (33.33%)  2
Vomiting * 1  1/4 (25.00%)  1 2/6 (33.33%)  2
General disorders     
Edema, trunk * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Fever * 1  2/4 (50.00%)  3 1/6 (16.67%)  1
Infections and infestations     
Enterocolitis, infectious * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Infections and infestations, other * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Lip infection * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Lung Infection * 1  0/4 (0.00%)  0 2/6 (33.33%)  2
Mucosal infection * 1  1/4 (25.00%)  3 2/6 (33.33%)  3
Periorbital infection * 1  1/4 (25.00%)  2 0/6 (0.00%)  0
Sepsis * 1  1/4 (25.00%)  1 3/6 (50.00%)  3
Sinusitis * 1  0/4 (0.00%)  0 2/6 (33.33%)  2
Skin infection * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Upper respiratory infection * 1  1/4 (25.00%)  1 3/6 (50.00%)  3
Wound infection * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Investigations     
Alanine aminotransferase increased * 1  1/4 (25.00%)  3 3/6 (50.00%)  9
Aspartate aminotransferase increased * 1  2/4 (50.00%)  8 3/6 (50.00%)  7
Blood bilirubin, increased * 1  1/4 (25.00%)  3 1/6 (16.67%)  1
CPK increased * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Fibrinogen, decreased * 1  0/4 (0.00%)  0 2/6 (33.33%)  4
GGT, increased * 1  1/4 (25.00%)  1 2/6 (33.33%)  2
INR increased * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Lipase increased * 1  1/4 (25.00%)  2 2/6 (33.33%)  4
Lymphocyte count decreased * 1  2/4 (50.00%)  14 3/6 (50.00%)  14
Neutrophil count, decreased * 1  2/4 (50.00%)  7 3/6 (50.00%)  7
Platelet count, decreased * 1  3/4 (75.00%)  43 3/6 (50.00%)  43
Serum amylase, increased * 1  0/4 (0.00%)  0 1/6 (16.67%)  3
White blood cell decreased * 1  2/4 (50.00%)  7 3/6 (50.00%)  17
Metabolism and nutrition disorders     
Acidosis * 1  1/4 (25.00%)  4 1/6 (16.67%)  1
Anorexia * 1  1/4 (25.00%)  1 2/6 (33.33%)  2
Dehydration * 1  1/4 (25.00%)  2 1/6 (16.67%)  1
Hypercalcemia * 1  1/4 (25.00%)  4 0/6 (0.00%)  0
Hyperglycemia * 1  3/4 (75.00%)  5 5/6 (83.33%)  19
Hyperkalemia * 1  2/4 (50.00%)  2 4/6 (66.67%)  7
Hypernatremia * 1  0/4 (0.00%)  0 2/6 (33.33%)  5
Hypertriglyceridemia * 1  1/4 (25.00%)  2 3/6 (50.00%)  12
Hyperuricemia * 1  1/4 (25.00%)  1 2/6 (33.33%)  2
Hypoalbuminemia * 1  2/4 (50.00%)  7 5/6 (83.33%)  8
Hypocalcemia * 1  3/4 (75.00%)  9 3/6 (50.00%)  13
Hypoglycemia * 1  2/4 (50.00%)  4 2/6 (33.33%)  3
Hypokalemia * 1  4/4 (100.00%)  29 5/6 (83.33%)  26
Hypophosphatemia * 1  3/4 (75.00%)  8 5/6 (83.33%)  14
Tumor lysis syndrome * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Nervous system disorders     
Intracranial hemorrhage * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Nervous system disorders, other * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Neuralgia * 1  0/4 (0.00%)  0 3/6 (50.00%)  3
Reversible posterior leukoencephalopathy syndrome * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Seizure * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Psychiatric disorders     
Agitation * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Anxiety * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Renal and urinary disorders     
Acute kidney injury * 1  1/4 (25.00%)  2 0/6 (0.00%)  0
Cystitis noninfective * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Urinary retention * 1  2/4 (50.00%)  2 2/6 (33.33%)  2
Urinary tract obstruction * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome * 1  1/4 (25.00%)  1 0/6 (0.00%)  0
Apnea * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Aspiration * 1  0/4 (0.00%)  0 1/6 (16.67%)  3
Atelectasis * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Bronchial stricture * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Bronchopulmonary hemorrhage * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Hypoxia * 1  3/4 (75.00%)  4 6/6 (100.00%)  13
Pleural effusion * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
Pulmonary edema * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Respiratory failure * 1  0/4 (0.00%)  0 2/6 (33.33%)  3
Stridor * 1  0/4 (0.00%)  0 2/6 (33.33%)  2
Wheezing * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Vascular disorders     
Hematoma * 1  0/4 (0.00%)  0 1/6 (16.67%)  1
Hypertension * 1  2/4 (50.00%)  3 4/6 (66.67%)  8
Hypotension * 1  1/4 (25.00%)  1 1/6 (16.67%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
The study was terminated early, because accrual goals were no longer feasible based on restrictions imposed by the Data Safety Monitoring Board (DSMB).
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Tanja A. Gruber, MD, PhD
Organization: St. Jude Children's Research Hospital
Phone: 901-595-2252
EMail: tanja.gruber@stjude.org
Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT02419755     History of Changes
Other Study ID Numbers: RELMLL
NCI-2015-00602 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Submitted: April 14, 2015
First Posted: April 17, 2015
Results First Submitted: November 8, 2017
Results First Posted: February 1, 2018
Last Update Posted: March 7, 2018