Skip to content

Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

A Phase II Pilot Study of Bortezomib (PS-341, Velcade) Combined With Reinduction Chemotherapy in Children and Young Adults With Recurrent, Refractory or Secondary Acute Myeloid Leukemia

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00666588
Enrollment
52
Registered
2008-04-25
Start date
2008-04-30
Completion date
2012-12-31
Last updated
2018-05-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myelomonocytic Leukemia (M4), Childhood Acute Basophilic Leukemia, Childhood Acute Eosinophilic Leukemia, Childhood Acute Erythroleukemia (M6), Childhood Acute Megakaryocytic Leukemia (M7), Childhood Acute Minimally Differentiated Myeloid Leukemia (M0), Childhood Acute Monoblastic Leukemia (M5a), Childhood Acute Monocytic Leukemia (M5b), Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Myeloblastic Leukemia Without Maturation (M1), Childhood Acute Myelomonocytic Leukemia (M4), Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia

Brief summary

This phase II trial is studying the side effects and best dose of bortezomib and to see how well it works when given together with combination chemotherapy in treating younger patients with recurrent, refractory, or secondary acute myeloid leukemia (AML). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin, cytarabine, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells

Detailed description

PRIMARY OBJECTIVES: I. To determine the toxicities and tolerability of bortezomib in combination with standard-relapse AML therapy (idarubicin/cytarabine or etoposide/high-dose cytarabine) in pediatric and young adult patients with relapsed or primary-refractory or secondary AML. II. To estimate the complete response rate to the Arm A and Arm B regimens. SECONDARY OBJECTIVES: I. To determine whether bortezomib inhibits proteasome activity, NF-kB activity and induces apoptosis pathway proteins in leukemia myeloblasts. II. To determine the feasibility of measuring AML stem cells in relapsed and recovering bone marrow. OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are stratified according to anthracycline\*-equivalent cumulative exposure (≤ 400 mg/m² vs \> 400 mg/m²). Patients are assigned to 1 of 2 groups. GROUP I (efficacy phase, patients with ≤ 400 mg/m² anthracycline-equivalent cumulative exposure - Closed as of 08/01/10): Patients receive idarubicin IV over 15 minutes on days 1-3, low-dose cytarabine IV continuously over days 1-7, and bortezomib IV on days 1, 4, and 8. GROUP II (dose-finding phase (closed as of 10/10) and efficacy phase, patients with \> 400 mg/m² anthracycline\*-equivalent cumulative exposure): Patients receive etoposide IV over 1 hour on days 1-5, high-dose cytarabine IV over 1 hour twice daily on days 1-5, and bortezomib IV on days 1, 4, and 8. NOTE: \* Anthracycline restriction no longer required for group 2 as of 10/02/10. All patients receive intrathecal cytarabine prior to courses 1 and 2. In both arms, treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically for at least 5 years.

Interventions

DRUGetoposide

Given IV

OTHERlaboratory biomarker analysis

Correlative studies

DRUGidarubicin

Given IV

DRUGcytarabine

Given IV or IT

DRUGbortezomib

Given IV

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No

Inclusion criteria

* Diagnosis of acute myeloid leukemia (AML) according to WHO classification * At least 5% blasts in the bone marrow * With or without extramedullary disease * To be eligible for the dose-finding phase (closed as of 10/10) : * Relapsed patients must meet the following criteria: * Must have had a prior diagnosis of AML, but may NOT have inv(16) or t(8;21) cytogenetics * May be in first or any subsequent relapse * If in first relapse, remission duration must be less than one year * Refractory patients must meet the following criteria: * Must have had a prior diagnosis of AML * May have received one or more attempt at remission induction * Patients with treatment-related AML may be previously treated or untreated for secondary AML * To be eligible for the efficacy phase: * Relapsed patients must meet the following criteria: * Must have had a prior diagnosis of AML, with no restriction on prior cytogenetics * Must be in first relapse * Must not have received prior reinduction therapy * Refractory patients must meet the following criteria: * Must have had a prior diagnosis of AML * Must not have received more than one attempt at remission induction (which may consist of up to two therapy courses) * Patients with treatment-related AML must be previously untreated for secondary AML * No juvenile myelomonocytic leukemia or acute promyelocytic leukemia (APL; FAB M3) * Patients with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: * CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs * CNS 2, defined as presence of \< 5/μL WBCs in CSF and cytospin positive for blasts, or \> 5/uL WBCs but negative by Steinherz/Bleyer algorithm: * CNS 2a: \< 10/μL RBCs; \< 5/μL WBCs and cytospin positive for blasts * CNS 2b: ≥ 10/μL RBCs; \< 5/μL WBCs and cytospin positive for blasts * CNS 2c: ≥ 10/μL RBCs; ≥ 5/μL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm * Patients with CNS3 disease (presence of ≥ 5/μL WBCs in CSF and cytospin positive for blasts \[in the absence of a traumatic lumbar puncture\] and/or clinical signs of CNS leukemia) are not eligible * CNS toxicity ≤ grade 2 * Lansky (patients ≤ 16 years of age) or Karnofsky (patients \> 16 years of age) performance status (PS) 50-100% * ECOG PS 0-2 * No Down syndrome * No Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome * No evidence of active graft-vs-host disease * Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age/gender as follows: * 0.4 mg/dL for patients 1 month to \< 6 months of age * 0.5 mg/dL for patients 6 months to \< 1 year of age * 0.6 mg/dL for patients 1 to \< 2 years of age * 0.8 mg/dL for patients 2 to \< 6 years of age * 1 mg/dL for patients 6 to \< 10 years of age * 1.2 mg/dL for patients 10 to \< 13 years of age * 1.5 mg/dL (male) or 1.4 mg/dL (female) for patients 13 to \< 16 years of age * 1.7 mg/dL (male) or 1.4 mg/dL (female) for patients ≥ 16 years of age * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * ALT \< 3.0 times ULN for age (unless elevation due to leukemia involvement) * Shortening fraction ≥ 27% by ECHO OR LVEF ≥ 50% by gated radionuclide * Normal respiratory rate and pulse oximetry \> 94% on room air * FEV\_1 ≥ 80% of predicted * FVC and DLCO \> 50% (corrected for hemoglobin) * Patients who are unable to perform pulmonary function tests (PFTs) (e.g., because of young age) will be excluded provided they have a medical history of significant prior pulmonary events or chronic pulmonary disease (e.g., pneumonia requiring mechanical ventilation support, pulmonary GVHD, pneumonectomy, or pulmonary toxin exposure) * Children with histories of resolved bronchiolitis, resolved viral pneumonias and well-controlled asthma are eligible, even if they are unable to perform PFTs * Patients with seizure disorder may be enrolled if on a non-enzyme-inducing anticonvulsant and if seizures are well-controlled * No uncontrolled infection * No known allergy to idarubicin, cytarabine, etoposide, boron, mannitol or bortezomib * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Concurrent radiotherapy allowed for patients who present with a chloroma that is producing or threatens to produce an irreversible neurologic deficit * Recovered from all prior chemotherapy, immunotherapy, or radiotherapy * More than 2 weeks since prior cytotoxic chemotherapy (4 weeks for nitrosoureas), except for hydroxyurea, which is allowed up to 24 hours prior to first dose of study drug, and intrathecal chemotherapy, which is allowed immediately up to administration of study drug * Prior steroid allowed as clinically indicated for patients with asthma * Hydrocortisone and methylprednisolone allowed as premedication in patients with a history of severe allergic reactions * At least 7 days since prior biologic agents, such as steroids, retinoids, or donor lymphocyte infusion without conditioning * At least 2 weeks since prior local palliative radiotherapy (small port) * At least 8 weeks since prior craniospinal radiotherapy or ≥ 50% radiation of pelvis * At least 6 weeks since prior other bone marrow radiation * At least 1 day since prior green tea containing products, any products containing vitamin C, flavanoids or other antioxidants (e.g., vitamins, herbal supplements), and foods with high vitamin C content * No prior radiotherapy to \> 25% of lung volume * No prior total-body irradiation as part of a hematopoietic stem cell conditioning regimen * At least 2 months since prior stem cell transplantation * No concurrent graft-vs-host disease prophylactic medication * No prior bortezomib or other proteasome inhibitors * No other concurrent investigational drugs * More than 4 days since prior growth factors that support platelet or white cell number or function * No concurrent enzyme-inducing anticonvulsant medications known to be potent inducers of the cytochrome P450 system, including phenytoin, carbamazepine, and phenobarbital * Concurrent benzodiazepines and gabapentin allowed * No concurrent grapefruit juice with bortezomib * No other concurrent cancer chemotherapy or immunomodulating agents * No concurrent corticosteroids as anti-emetic therapy * Concurrent corticosteroids therapy allowed as treatment or prophylaxis for anaphylactic reactions, symptoms of cytarabine syndrome, and as treatment for presumptive bortezomib-induced pulmonary toxicity.

Design outcomes

Primary

MeasureTime frameDescription
Dose Limiting ToxicityDuring Course 1Number of participants with dose limiting toxicity.
Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1After course 1Overall response (complete remission \[CR\] and CR with partial recovery \[CRp\]) during course 1.

Secondary

MeasureTime frameDescription
NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)At baseline, prior to and up to 24 hours after bortezomib treatmentNF-kB activity will be measured as a continuous variable (ng NF-kB/Mg protein). Differences in NF-κB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range. We may perform exploratory analyses to determine if single time point measurements, or the difference between time points, correlate with treatment response.
Proteasome Inhibition ActivityAt baselineMean and standard deviation of β1 and β5- Results are ratios (proteasome subunit/β-actin based on loading of 15 µg total protein, normalized to CEM).
Protein Expression Assessed by Western BlotAt baseline, prior to and up to 24 hours after bortezomib treatmentRelative expression of apoptotic and cell cycle proteins will be characterized using descriptive statistics. If differences are noted between pre and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test if the data are non-normally distributed. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.
Feasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionAt baseline and after completion of course 1Descriptive statistics to assess mean +/- standard deviation for the percentage leukemia initiation cells (LIC) depletion.

Countries

Australia, Canada, United States

Participant flow

Participants by arm

ArmCount
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure
Bortezomib 1.3mg/m2 to assess efficacy in low prior anthracycline exposure. Patients receive idarubicin IV (12 mg/m2/day) over 15 minutes on days 1-3, low-dose cytarabine IV (100 mg/m2/day) continuously over days 1-7, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (closed as of 08/01/10). Dosage modification based on age \< 3 years old. idarubicin: Given IV cytarabine: Given IV or IT bortezomib: Given IV laboratory biomarker analysis: Correlative studies
18
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp
Bortezomib 1.0 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.0 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. cytarabine: Given IV or IT bortezomib: Given IV etoposide: Given IV laboratory biomarker analysis: Correlative studies
6
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp
Bortezomib 1.3 mg/m2 to assess feasibility in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity (dose-finding phase closed as of 10/10). cytarabine: Given IV or IT bortezomib: Given IV etoposide: Given IV laboratory biomarker analysis: Correlative studies
6
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp
Bortezomib 1.3 mg/m2 to assess efficacy in high prior anthracycline exposure. Patients receive etoposide IV (150 mg/m2/dose) over 1 hour on days 1-5, high-dose cytarabine IV (1000 mg/m2/dose) over 1 hour twice daily on days 1-5, and bortezomib IV (1.3 mg/m2) on days 1, 4, and 8. All patients receive intrathecal cytarabine (30 mg - age 1-1.99 years, 50 mg - age 2-2.99 years, 70 mg - age ≥ 3 years) prior to courses 1 and 2. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity cytarabine: Given IV or IT bortezomib: Given IV etoposide: Given IV laboratory biomarker analysis: Correlative studies
22
Total52

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall Studyineligible2002
Overall Studyinevaluable2000

Baseline characteristics

CharacteristicBortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureBortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpBortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpBortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpTotal
Age, Categorical
<=18 years
15 Participants4 Participants6 Participants21 Participants46 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
3 Participants2 Participants0 Participants1 Participants6 Participants
Age, Continuous4121.72 days
STANDARD_DEVIATION 2569.95
5637.0 days
STANDARD_DEVIATION 1757.39
2812.5 days
STANDARD_DEVIATION 1769.83
3365.0 days
STANDARD_DEVIATION 2227.99
3984.06 days
STANDARD_DEVIATION 2081.29
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants0 Participants1 Participants3 Participants7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
13 Participants6 Participants5 Participants17 Participants41 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants0 Participants0 Participants2 Participants4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants2 Participants1 Participants1 Participants5 Participants
Race (NIH/OMB)
Black or African American
3 Participants1 Participants1 Participants2 Participants7 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants0 Participants1 Participants1 Participants5 Participants
Race (NIH/OMB)
White
11 Participants3 Participants3 Participants18 Participants35 Participants
Region of Enrollment
Australia
0 participants0 participants0 participants1 participants1 participants
Region of Enrollment
Canada
1 participants1 participants0 participants1 participants3 participants
Region of Enrollment
United States
17 participants5 participants6 participants20 participants48 participants
Sex: Female, Male
Female
11 Participants2 Participants4 Participants13 Participants30 Participants
Sex: Female, Male
Male
7 Participants4 Participants2 Participants9 Participants22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
14 / 165 / 65 / 614 / 20
serious
Total, serious adverse events
3 / 163 / 61 / 65 / 20

Outcome results

Primary

Dose Limiting Toxicity

Number of participants with dose limiting toxicity.

Time frame: During Course 1

ArmMeasureValue (NUMBER)
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureDose Limiting Toxicity0 participants
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpDose Limiting Toxicity1 participants
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpDose Limiting Toxicity0 participants
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpDose Limiting Toxicity0 participants
Primary

Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1

Overall response (complete remission \[CR\] and CR with partial recovery \[CRp\]) during course 1.

Time frame: After course 1

ArmMeasureValue (NUMBER)
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureOverall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 14 participants
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpOverall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 12 participants
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpOverall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 12 participants
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpOverall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 19 participants
Secondary

Feasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) Depletion

Descriptive statistics to assess mean +/- standard deviation for the percentage leukemia initiation cells (LIC) depletion.

Time frame: At baseline and after completion of course 1

Population: Ineligible patients (n=4) are excluded. Patients without available data (n=42) are excluded.

ArmMeasureGroupValue (MEAN)Dispersion
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPrior to Treatment0.013667 percentage of LIC depletionStandard Deviation 0.02108
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPost Treatment0.021 percentage of LIC depletionStandard Deviation 0.036373
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPrior to Treatment0.2 percentage of LIC depletion
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPost Treatment0.43 percentage of LIC depletion
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPrior to Treatment1.6385 percentage of LIC depletionStandard Deviation 2.06887
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpFeasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) DepletionPost Treatment0.0435 percentage of LIC depletionStandard Deviation 0.0615183
Secondary

NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)

NF-kB activity will be measured as a continuous variable (ng NF-kB/Mg protein). Differences in NF-κB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range. We may perform exploratory analyses to determine if single time point measurements, or the difference between time points, correlate with treatment response.

Time frame: At baseline, prior to and up to 24 hours after bortezomib treatment

Population: Ineligible patients (n=4) are excluded. Patients without available data (n=36) are excluded.

ArmMeasureGroupValue (MEAN)Dispersion
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)Baseline718.218 ng/Mg proteinStandard Deviation 418.149339
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)24 Hrs after treatment774.1925 ng/Mg proteinStandard Deviation 410.667711
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)24 Hrs after treatment345.46 ng/Mg protein
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)Baseline655.4 ng/Mg protein
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)Baseline974.66 ng/Mg protein
Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)24 Hrs after treatment855.96 ng/Mg protein
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)Baseline408.144 ng/Mg proteinStandard Deviation 484.084297
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpNF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)24 Hrs after treatment497.31 ng/Mg proteinStandard Deviation 449.312899
Secondary

Proteasome Inhibition Activity

Mean and standard deviation of β1 and β5- Results are ratios (proteasome subunit/β-actin based on loading of 15 µg total protein, normalized to CEM).

Time frame: At baseline

Population: Ineligible patients (n=4) are excluded. Patients without available data (n=36) are excluded. The data summarized are only at baseline as that is the only data available.

ArmMeasureGroupValue (MEAN)Dispersion
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureProteasome Inhibition ActivityBaseline β10.08115 ratioStandard Deviation 0.0860893
Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline ExposureProteasome Inhibition ActivityBaseline β50.121575 ratioStandard Deviation 0.0691725
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpProteasome Inhibition ActivityBaseline β10.7894 ratio
Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline ExpProteasome Inhibition ActivityBaseline β50.2576 ratio
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpProteasome Inhibition ActivityBaseline β10.2895143 ratioStandard Deviation 0.2974052
Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline ExpProteasome Inhibition ActivityBaseline β50.3721286 ratioStandard Deviation 0.7140883
Secondary

Protein Expression Assessed by Western Blot

Relative expression of apoptotic and cell cycle proteins will be characterized using descriptive statistics. If differences are noted between pre and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test if the data are non-normally distributed. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.

Time frame: At baseline, prior to and up to 24 hours after bortezomib treatment

Population: These data will never be collected because the investigators decided not to perform quantitative biologic analysis.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026