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Trial record 24 of 325 for:    "Acute Lymphocytic Leukemia" | "Methotrexate"

Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

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ClinicalTrials.gov Identifier: NCT01312818
Recruitment Status : Terminated (Slow accrual)
First Posted : March 11, 2011
Results First Posted : May 15, 2015
Last Update Posted : December 28, 2017
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Lymphoblastic Leukemia
Interventions Drug: Bortezomib
Drug: Vorinostat
Drug: Dexamethasone
Drug: Methotrexate
Drug: Imatinib mesylate
Enrollment 2
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Chemotherapy
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bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate.

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Period Title: Overall Study
Started 2
Completed 2
Not Completed 0
Arm/Group Title Chemotherapy
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bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate.

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Overall Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
<=18 years
2
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
0
   0.0%
Male
2
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants
2
1.Primary Outcome
Title Number of Subjects Who Achieved Complete Remission of Their Disease
Hide Description Complete Remission (CR): A CR requires that the following be recorded concurrently: an absolute neutrophil count (segs and bands) > 1000/μL, no circulating blasts, platelets > 100,000/μL; adequate bone marrow cellularity with trilineage hematopoiesis, and < 5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent. If patients continue on with treatment, there can be no evidence of recurrence of ALL for at least 4 weeks.
Time Frame Day 30
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title ALL Treated Patients
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bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate.

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
0
2.Secondary Outcome
Title Number of Subjects Experiencing Drug Related Adverse Events
Hide Description To characterize the toxicities of bortezomib, vorinostat and dexamethasone when used in combination. Toxicity will be graded using the NCI’s Common Terminology Criteria for Adverse Events (CTCAE 4.0).
Time Frame Day 1 of Treatment to 30 Days Post Treatment
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title ALL Treated Patients
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List of toxicities in acute lymphoblastic leukemia (ALL) patients treated with bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate.

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
1
3.Secondary Outcome
Title Number of Subjects With Activated Caspases and Other Regulators of Apoptosis
Hide Description Activation of caspases and other regulators of apoptosis in treated blast cells will be determined by Western analysis (correlative lab analysis).
Time Frame From Day 1 to 30 Days After Last Dose
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Hide Analysis Population Description
The trial was terminated early with only 2 patients so caspase samples were not sent for analysis.
Arm/Group Title Chemotherapy
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Bortezomib IV Vorinostat PO Dexamethasone PO Intrathecal Methotrexate Imatinib Mesylate PO (for Ph+ ALL patients only)

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Chemotherapy
Hide Arm/Group Description

bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate.

Bortezomib: 1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

Vorinostat: 180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

Dexamethasone: 6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

Imatinib mesylate: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

All-Cause Mortality
Chemotherapy
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Chemotherapy
Affected / at Risk (%) # Events
Total   1/2 (50.00%)    
Blood and lymphatic system disorders   
death from disease  1  1/2 (50.00%)  1
Gastrointestinal disorders   
esophageal ulcer  1  1/2 (50.00%)  1
Infections and infestations   
Sepsis  1  1/2 (50.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v.4
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Chemotherapy
Affected / at Risk (%) # Events
Total   2/2 (100.00%)    
Gastrointestinal disorders   
Gastric hemorrhage   1/2 (50.00%)  1
Gastric ulcer   1/2 (50.00%)  1
General disorders   
Fever   1/2 (50.00%)  1
Investigations   
Alanine aminotransferase increased   1/2 (50.00%)  1
Aspartate aminotransferase increased   1/2 (50.00%)  1
Investigations - Other, specify: hyperphosphatemia   1/2 (50.00%)  1
Metabolism and nutrition disorders   
Hyponatremia   1/2 (50.00%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea   1/2 (50.00%)  1
Hypoxia   1/2 (50.00%)  1
Respiratory failure   1/2 (50.00%)  1
Vascular disorders   
Hypotension   1/2 (50.00%)  1
Indicates events were collected by systematic assessment
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: Dr. Michael Burke, MD
Organization: University of Minnesota, Pediatric Hematology Dept.
Phone: 612-672-7422
Layout table for additonal information
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01312818     History of Changes
Other Study ID Numbers: 2008LS113
MT2008-33R ( Other Identifier: Blood and Bone Marrow Transplantation Program )
1010M91973 ( Other Identifier: IRB, University of Minnesota )
X05323 ( Other Identifier: Millennium Pharmaceuticals, Inc. )
First Submitted: March 9, 2011
First Posted: March 11, 2011
Results First Submitted: April 22, 2015
Results First Posted: May 15, 2015
Last Update Posted: December 28, 2017