Leukemia-Lymphoma, Adult T-Cell
Conditions
Brief summary
The rationale of the current study is to explore the use of combination chemotherapy together with antiretroviral agents in order to determine the efficacy and toxicity of this approach, while also examining markers of virus replication and expression, and tumor cell proliferation to gain understanding of the biological basis of this malignancy and to identify predictors of response.
Detailed description
Primary Endpoint: \- To determine the tolerability and efficacy (response rate) of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in patients with HTLV-1 associated leukemia/lymphoma (ATLL). Secondary Endpoints: * To evaluate the effects of DA B-EPOCH chemotherapy combined with Raltegravir on HTLV-1 DNA and RNA load, HTLV-1 integrase gene sequence, and HTLV-1 integration sites. To determine if relapsed or progressive disease is a result of renewed virus replication. * To evaluate the relation of NFκB gene expression profile on response to DA B-EPOCH chemotherapy combined with Raltegravir.
Interventions
DRUGBortezomib
DRUGEtoposide
DRUGVincristine
DRUGDoxorubicin
DRUGPrednisone
DRUGCyclophosphamide
DRUGRaltegravir
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented ATLL. Patients with previously untreated or treated ATLL are eligible. * Tumors must be CD3 positive (\>50% cells express CD3). * Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Western blot) Confirmation of HTLV-1 rather than HTLV-2 by differential Western blot (e.g. Genelabs Diagnostics HTLV Blot 2.4) or PCR is desirable but his result is not required prior to trial enrollment. * Measurable disease must be present. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least two perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.For patients with acute (leukemic) form of ATLL, measureable disease can be derived from CD4+ lymphocyte flow data on the peripheral blood and/or bone marrow. * All stages are eligible. * Adequate hematologic function within 14 days before enrollment: ANC\>1000 cells/mm3, platelet count\>75,000 cells/mm3 unless cytopenias are secondary to ATLL. All patients must be off hematologic growth factors for at least 24 hrs. * Adequate hepatic function, transaminase \<3 times the upper limit of normal unless due to to Gilbert's disease or hepatic involvement by tumor; total bilirubin ≤1.5 times the upper limit of normal * Creatinine\<2.0 unless due to lymphoma. * Karnofsky Performance Status (KPS) at least 50 * Age at least 18. -Voluntary written informed consent before performance of any study- related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Female patients of child bearing potential must have a negative pregnancy test within 72 hrs of initiation of therapy. Female patients are either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study. Male patients must agree to use two acceptable methods for contraception for the duration of the study. Women must avoid pregnancy and men avoid fathering children while in the study. * HIV positive patients are eligible if they are receiving at least two other active anti-HIV therapies other than zidovudine or atazanavir. * Patients with active hepatitis B (HBV) infection are eligible if they are receiving effective anti-HBV therapy. * Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial.
Exclusion criteria
* Acute active infection requiring acute therapy. Chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met. * Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Women who are pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patient has ≥Grade 2 peripheral neuropathy * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant. * Patient has hypersensitivity to bortezomib, boron or mannitol. * Patient has received other investigational drugs with 14 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * 1.5x upper limit of normal (ULN) total bilirubin except if is determined to be related to Gilbert's disease or tumor biliary/liver involvement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Up to 30 days after completion of treatment | The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting. |
| Efficacy of Treatment as Measured by Best Overall Response | Up to 4 years following completion of therapy | -The response definitions used for this study are the 2007 Cheson criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relation of NFκB Gene Expression Profile on Response | 6 months | Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated. |
| Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA | 6 months | — |
| Time to Progression | Up to 4 years following completion of therapy | -The progression definitions used for this study are from the 2007 Cheson criteria. |
| Effects of HTLV-1 Integration Sites After Treatment | 6 months | — |
| Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence | 6 months | — |
| Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads | 6 months | — |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on 12/22/2010 and closed to participant enrollment on 05/29/2014.
Participants by arm
| Arm | Count |
|---|---|
| Acute ATLL Bortezomib 1.0 mg/m2 IV Days 1-4
Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4
Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4
Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4
Prednisone 60 mg/m2/d PO on Days 1-5
Cyclophosphamide 375 mg/m2 IV on Day 5
Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle.
Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles. | 6 |
| Lymphoma ATLL Bortezomib 1.0 mg/m2 IV Days 1-4
Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4
Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4
Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4
Prednisone 60 mg/m2/d PO on Days 1-5
Cyclophosphamide 375 mg/m2 IV on Day 5
Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle.
Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles. | 12 |
| Total | 18 |
Baseline characteristics
| Characteristic | Lymphoma ATLL | Total | Acute ATLL |
|---|---|---|---|
| Age, Continuous | 56 years | 52 years | 51.5 years |
| Birthplace Antigua | 1 participants | 1 participants | 0 participants |
| Birthplace Bahamas | 0 participants | 1 participants | 1 participants |
| Birthplace Dominican Republic | 0 participants | 1 participants | 1 participants |
| Birthplace Haiti | 3 participants | 3 participants | 0 participants |
| Birthplace Jamaica | 5 participants | 8 participants | 3 participants |
| Birthplace USA | 2 participants | 3 participants | 1 participants |
| Birthplace Virgin Islands | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 12 participants | 18 participants | 6 participants |
| Sex: Female, Male Female | 10 Participants | 14 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
Efficacy of Treatment as Measured by Best Overall Response
-The response definitions used for this study are the 2007 Cheson criteria.
Time frame: Up to 4 years following completion of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Efficacy of Treatment as Measured by Best Overall Response | Progressive Disease | 3 participants |
| EPOCH Chemotherapy & Bortezomib | Efficacy of Treatment as Measured by Best Overall Response | Stable disease | 3 participants |
| EPOCH Chemotherapy & Bortezomib | Efficacy of Treatment as Measured by Best Overall Response | Partial response | 9 participants |
| EPOCH Chemotherapy & Bortezomib | Efficacy of Treatment as Measured by Best Overall Response | Complete response | 3 participants |
Primary
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
Time frame: Up to 30 days after completion of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Fatigue | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Vomiting | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Spontaneous bacterial peritonitis | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Abdominal distension | 2 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hemoglobin | 6 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Leukocytes (WBC) | 7 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Lymphopenia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Neutrophils | 6 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Platelets | 6 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Infection without neutropenia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Infection with neutropenia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Omaya port infection | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | IV port infection | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Sepsis | 2 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Neutropenic fever | 3 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypoglycemia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hyperglycemia | 2 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Magnesium | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypokalemia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypertriglyceridemia | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Confusion | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Headache | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Encephalitis | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Abdominal pain | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Cough | 1 participants |
| EPOCH Chemotherapy & Bortezomib | Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Dyspnea | 1 participants |
Secondary
Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence | Baseline | 0.49 percentage of nucleotide divergence | Standard Error 0.05 |
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence | Study completion | 0.52 percentage of nucleotide divergence | Standard Error 0.06 |
Secondary
Effects of HTLV-1 Integration Sites After Treatment
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 Integration Sites After Treatment | Baseline | 1.31 number of integration sites | Standard Error 0.31 |
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 Integration Sites After Treatment | Study completion | 1.00 number of integration sites | Standard Error 0.22 |
Secondary
Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA | Study completion | 7.33 copies/peripheral blood mononuclear cell | Standard Error 2.76 |
| EPOCH Chemotherapy & Bortezomib | Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA | Baseline | 37.0 copies/peripheral blood mononuclear cell | Standard Error 11.9 |
| Non-responders | Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA | Baseline | 41.9 copies/peripheral blood mononuclear cell | Standard Error 29.1 |
| Non-responders | Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA | Study completion | 35.7 copies/peripheral blood mononuclear cell | Standard Error 23.7 |
Secondary
Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads | Baseline | 0.372 copies/peripheral blood mononuclear cell | Standard Error 0.123 |
| EPOCH Chemotherapy & Bortezomib | Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads | Study completion | 0.0128 copies/peripheral blood mononuclear cell | Standard Error 0.023 |
| Non-responders | Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads | Baseline | 0.417 copies/peripheral blood mononuclear cell | Standard Error 0.045 |
| Non-responders | Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads | Study completion | 0.033 copies/peripheral blood mononuclear cell | Standard Error 0.147 |
Secondary
Relation of NFκB Gene Expression Profile on Response
Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.
Time frame: 6 months
Population: Average RPKM values normalized to Patient A before therapy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Relation of NFκB Gene Expression Profile on Response | CD45 | 1.000 fold expression | Standard Error 0 |
| EPOCH Chemotherapy & Bortezomib | Relation of NFκB Gene Expression Profile on Response | BLK | 1.000 fold expression | Standard Error 0 |
| EPOCH Chemotherapy & Bortezomib | Relation of NFκB Gene Expression Profile on Response | CD4 | 1.000 fold expression | Standard Error 0 |
| EPOCH Chemotherapy & Bortezomib | Relation of NFκB Gene Expression Profile on Response | CADMI | 1.000 fold expression | Standard Error 0 |
| EPOCH Chemotherapy & Bortezomib | Relation of NFκB Gene Expression Profile on Response | CD25 | 1.000 fold expression | Standard Error 0 |
| Non-responders | Relation of NFκB Gene Expression Profile on Response | CADMI | 0.011 fold expression | Standard Error 0.001 |
| Non-responders | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.035 fold expression | Standard Error 0.006 |
| Non-responders | Relation of NFκB Gene Expression Profile on Response | CD45 | 1.718 fold expression | Standard Error 0.045 |
| Non-responders | Relation of NFκB Gene Expression Profile on Response | CD4 | 1.380 fold expression | Standard Error 0.047 |
| Non-responders | Relation of NFκB Gene Expression Profile on Response | BLK | 0.178 fold expression | Standard Error 0.015 |
| Patient B (Responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 2.049 fold expression | Standard Error 0.035 |
| Patient B (Responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 0.889 fold expression | Standard Error 0.15 |
| Patient B (Responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 0.623 fold expression | Standard Error 0.031 |
| Patient B (Responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.303 fold expression | Standard Error 0.013 |
| Patient B (Responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 1.437 fold expression | Standard Error 0.08 |
| Patient B (Responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 0.959 fold expression | Standard Error 0.016 |
| Patient B (Responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 0.172 fold expression | Standard Error 0.073 |
| Patient B (Responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 0.607 fold expression | Standard Error 0.023 |
| Patient B (Responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 0.007 fold expression | Standard Error 0.001 |
| Patient B (Responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.015 fold expression | Standard Error 0.003 |
| Patient C (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 68.856 fold expression | Standard Error 10.543 |
| Patient C (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 1.163 fold expression | Standard Error 0.021 |
| Patient C (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.862 fold expression | Standard Error 0.013 |
| Patient C (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 1.494 fold expression | Standard Error 0.19 |
| Patient C (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 1.319 fold expression | Standard Error 0.075 |
| Patient C (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 1.816 fold expression | Standard Error 0.105 |
| Patient C (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.691 fold expression | Standard Error 0.013 |
| Patient C (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 1.640 fold expression | Standard Error 0.039 |
| Patient C (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 1.923 fold expression | Standard Error 0.092 |
| Patient C (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 77.590 fold expression | Standard Error 12.715 |
| Patient D (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 2.013 fold expression | Standard Error 0.085 |
| Patient D (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 2.897 fold expression | Standard Error 0.098 |
| Patient D (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 233.179 fold expression | Standard Error 60.619 |
| Patient D (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 3.057 fold expression | Standard Error 0.34 |
| Patient D (Non-responder) Pre-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 0.594 fold expression | Standard Error 0.008 |
| Patient D (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD45 | 0.714 fold expression | Standard Error 0.019 |
| Patient D (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD4 | 0.648 fold expression | Standard Error 0.056 |
| Patient D (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | BLK | 46.801 fold expression | Standard Error 13.193 |
| Patient D (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CD25 | 0.512 fold expression | Standard Error 0.023 |
| Patient D (Non-responder) Post-Therapy | Relation of NFκB Gene Expression Profile on Response | CADMI | 0.470 fold expression | Standard Error 0.026 |
Secondary
Time to Progression
-The progression definitions used for this study are from the 2007 Cheson criteria.
Time frame: Up to 4 years following completion of therapy
Population: 12 out of the 18 participants had a complete or partial response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EPOCH Chemotherapy & Bortezomib | Time to Progression | Best response of complete response | 199 days |
| EPOCH Chemotherapy & Bortezomib | Time to Progression | Best response of partial response | 143 days |
| EPOCH Chemotherapy & Bortezomib | Time to Progression | Best response of stable disease | 88 days |
| EPOCH Chemotherapy & Bortezomib | Time to Progression | All participants | 127 days |