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| ID | Type | Description | Link |
|---|---|---|---|
| OSU 0491 | |||
| N01CM62207 | U.S. NIH Grant/Contract | View source |
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CTEP Initiated Action.
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This phase II trial is studying how well flavopiridol works in treating patients with chronic lymphocytic leukemia or prolymphocytic leukemia. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing
PRIMARY OBJECTIVES:
I. To determine the complete response (CR) and overall response rate (CR + Partial Response [PR]) of this regimen.
II. To assess the toxicity profile of this regimen. III. To examine response duration, progression-free survival and overall survival, following this treatment.
IV. To assess the pharmacokinetics of this novel schedule of administration.
SECONDARY OBJECTIVES:
I. To determine the influence of adverse prognostic factors including interphase cytogenetics, VH mutational status, ZAP-70 expression, CD38, and p53 mutational status with response to flavopiridol treatment.
II. To determine the influence of flavopiridol treatment on serial measurements of mcl-1 (mRNA and protein), HIF-1 (mRNA and protein), NF-kappaB activity, IkappaB, IkappaB phosphorylation, GSK-beta, and IL-6 down-stream targets.
III. To assess the relationship of drug induced apoptosis and mitochondrial perturbation of Chronic Lymphocytic Leukemia (CLL) cells in vitro and subsequent relationship to clinical response and tumor lysis in vivo.
IV. To examine cytokine levels (IL-6, IFN-gamma, TNF-alpha) during treatment with flavopiridol.
V. To assess pharmacokinetics (PK) to determine the variability of PK and PD analyses between treatment administrations and correlation with specific Single Nucleotide Polymorphisms (SNPs) potentially involved in flavopiridol disposition.
VI. To assess differences in diagnosis and relapse samples to investigate mechanisms of acquired flavopiridol resistance in primary CLL cells.
OUTLINE: This is an open-label study. Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22.
Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol.Patients are followed at 2 months and then every 3 months for 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (alvocidib) | Experimental | Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alvocidib | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response (CR) Rate | CR requires all of the following for at least two months from completion of therapy: Absence of lymphadenopathy in excess of 1 cm on physical exam; No hepatomegaly or splenomegaly on physical exam; Absence of constitutional symptoms; Normal CBC (complete blood count) as exhibited by polymorphonuclear leukocytes > 1500/µL, platelets > 100,000/µL, hemoglobin > 11.0 g/dl (untransfused); lymphocyte count < 5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with < 30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. | Up to 8 months |
| Overall Response Rate (CR + PR) | CR requires all of the following: Absence of lymphadenopathy in excess of 1 cm on physical exam; No hepatomegaly or splenomegaly on physical exam; Absence of constitutional symptoms; Normal CBC as exhibited by polymorphonuclear leukocytes > 1500/µL, platelets > 100,000/µL, hemoglobin > 11.0 g/dl (untransfused); lymphocyte count < 5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with < 30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. Patients with CR after induction but wih treatment-related persistent cytopenia is a PR. PR requires a > 50% decrease in peripheral lymphocyte count from pretreatment value, > 50% reduction in lymphadenopathy, and/or > 50% reduction in splenomegaly/hepatomegaly. These patients must have one of the following: polymorphonuclear leukocytes > 1,500/μL , platelets > 100,000/μL, hemoglobin > 11.0 g/dl (untransfused) or any with 50% improvement from pretreatment value. | Up to 8 months |
| Response Duration | Response evaluation criteria based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response. Descriptive statistics will be computed (median, range, mean, standard deviation, minimum, and maximum) on response duration. | Up to 8 months |
| Progression-free Survival (PFS) for Responding Patients as Assessed Using Standard Kaplan-Meier Methods |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) (AUC) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol | Pharmacokinetics were performed on day 1 and day 8 of cycle 1 by plasma levels of both flavopiridol and metabolites of flavopiridol using Area Under the Curve (AUC) | During treatment day 1 and day 8 of cycle 1 |
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Inclusion Criteria:
Histologically confirmed B-cell chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) arising from CLL
Requiring therapy, defined by any of the following:
Received ≥ 1 prior chemotherapy regimen that included fludarabine or nucleoside equivalent OR alternative therapy if contraindication to fludarabine exists (i.e., autoimmune hemolytic anemia)
Performance status - ECOG 0-2
More than 2 years
See Disease Characteristics
Baseline cytopenias allowed
WBC ≤ 200,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's disease, hemolysis, or disease infiltration of the liver)
AST ≤ 2 times ULN (unless due to hemolysis or disease infiltration of the liver)
Creatinine ≤ 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy that would limit life expectancy
See Disease Characteristics
No other concurrent chemotherapy
No concurrent chronic corticosteroids or corticosteroids as antiemetics
No concurrent hormonal therapy except steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes)
No concurrent radiotherapy
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| Name | Affiliation | Role |
|---|---|---|
| John Byrd | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio State University Medical Center | Columbus | Ohio | 43210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19826119 | Result | Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, Blum KA, Flynn JM, Jones JA, Hu W, Moran ME, Mitchell SM, Smith LL, Wagner AJ, Raymond CA, Schaaf LJ, Phelps MA, Villalona-Calero MA, Grever MR, Byrd JC. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009 Dec 10;27(35):6012-8. doi: 10.1200/JCO.2009.22.6944. Epub 2009 Oct 13. | |
| 24990615 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Alvocidib) | Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol.To improve tolerability of treatment regimen, an amendment to the protocol was done to reduce the cycle length from 42 days to 28 days, reducing the number of treatments per cycle from four (days 1, 8, 15 & 22) to three (days 1, 8, and 15). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Alvocidib) | Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Response (CR) Rate | CR requires all of the following for at least two months from completion of therapy: Absence of lymphadenopathy in excess of 1 cm on physical exam; No hepatomegaly or splenomegaly on physical exam; Absence of constitutional symptoms; Normal CBC (complete blood count) as exhibited by polymorphonuclear leukocytes > 1500/µL, platelets > 100,000/µL, hemoglobin > 11.0 g/dl (untransfused); lymphocyte count < 5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with < 30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. | Patients were assessed for clinical response after two, four and six cycles. | Posted | Number | percent of patients | Up to 8 months |
|
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NCI Common Toxicity Criteria of Adverse Events (version 3) and modified NCI Common Toxicity Criteria guidelines for evaluating hematologic toxicity for leukemia was used to grade adverse events for patients. Adverse events are reported across all grades.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Alvocidib) | Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE Version 3.0 | Systematic Assessment | Serious Adverse events reported were deaths |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Investigations | CTCAE Version 3.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Byrd, MD | The Ohio State University Comprehensive Cancer Center | 614-293-9869 | John.Byrd@osumc.edu |
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| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D015463 | Leukemia, Prolymphocytic |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C077990 | alvocidib |
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PFS was calculated from the date of study entry until time of disease progression or death, whichever came first, censoring patients alive and relapse free at last follow up. Patients who withdrew from study to undergo an allogeneic SCT (Stem cell transplantation) were censored at the time of transplantation.
| Up to 5 years |
| Progression-free Survival for All Patients as Assessed Using Standard Kaplan-Meier Methods | PFS was calculated from the date of study entry until time of disease progression or death, whichever came first, censoring patients alive and relapse free at last follow up. Patients who withdrew from study to undergo an allogeneic SCT were censored at the time of transplantation. | Up to 5 years |
| Overall Survival | Overall survival data will be reported on a 3-month basis for 5 years | Up to 5 years |
| Toxicity | Toxicity determination based on NCI Common Toxicity Criteria version 3 and modified NCI Common toxicity guidelines for evaluating hematologic toxicity in leukemia. | Measurement prior to each infusion, at end of therapy, 2 months post-completion and post-treatment follow-up every 3 months for two years. |
| PK (Cmax) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol |
Pharmacokinetics were performed on day 1 and day 8 of cycle 1 by plasma levels of both flavopiridol and metabolites of flavopiridol |
| During treatment day 1 and day 8 of course 1 |
| PK as Assessed by Levels of Both Flavopiridol and Metabolites of Flavopiridol in Urine Samples | urine samples were collected in some patients during the first 24 hours after the start of the infusion on cycle 1, day 1 to isolate metabolites of flavopiridol to be used as internal standard for plasma metabolite quantification experiments. | Urine collected at 4 separate times in some patients during the first 24 hours after start of infusion on day 1 of course 1. |
| Serial Levels of IL-6 as Assessed by Blood Plasma | IL-6 measures were adjusted for baseline values | 4.5 hours, 8 hours, 12 hours, and 24 hours following the initiation of therapy during day 1 of course 1 |
| Comparison of CLL Cell Samples Taken at Registration/Diagnosis to CLL Cell Samples Taken at Time of Relapse | Samples will be examined for ex vivo sensitivity to flavopiridol, expression of select anti-apoptosis proteins, BCRP mRNA and protein expression, difference in gene expression by cDNA microarray and potentially by epigenetic arrays. Comparisons will be used to evaluate mechanisms of acquired flavopiridol resistance. | At baseline and at time of relapse or when patient goes off therapy due to disease progression |
| Correlation of Adverse Prognostic Factors With Response to Flavopiridol Treatment as Assessed by Interphase Cytogenetics, VH Mutational Status, ZAP-70 Protein Expression, CD38, and p53 | overall response rates (CR+PR) | up to 8 months |
| Levels of Mcl-1 mRNA, Mcl-1 Protein, HIF-1alpha Protein, HIF-1alpha mRNA, NF-kappaB Activation, Total IkB, IkB Phosphorylation, GSK-beta Activity, and IL-6 Target Genes (i.e., STAT3) | Assessed by real time RT-PCR (mcl-1, HIF-1alpha), immunoblot analysis (mcl-1, HIF-1alpha, I-kappaB, I-kappaB phosphorylation, targets of IL-6), and electrophoretic mobility shift analysis (NF-kappaB activation) | At baseline, 4.5 hours (end of continuous infusion), 8 hours, and approximately 24 hours following initiation of therapy |
| Comparison of Clinical Response and Tumor Lysis in Vivo With Drug-induced Apoptosis and Mitochondrial Perturbation in Vitro as Assessed by Flow Cytometry | CLL cells will be incubated with control or flavopiridol (1 or 2.8 microMolar) for 4-hours followed by a 20 hours in media with 10% heat-inactivated human serum. Assessment of apoptosis following exposure of human CLL cells will be performed using annexin/PI flow cytometry. Patient samples with greater than 50% live cells (annexin-/PI-) following exposure to 2.8 microMolar flavopiridol will be considered to have insensitive disease. Patients whose CLL cells have less than 50% live cells at 1 microMolar will be considered to have highly sensitive disease. | At baseline |
| Pierceall WE, Warner SL, Lena RJ, Doykan C, Blake N, Elashoff M, Hoff DV, Bearss DJ, Cardone MH, Andritsos L, Byrd JC, Lanasa MC, Grever MR, Johnson AJ. Mitochondrial priming of chronic lymphocytic leukemia patients associates Bcl-xL dependence with alvocidib response. Leukemia. 2014 Nov;28(11):2251-4. doi: 10.1038/leu.2014.206. Epub 2014 Jul 3. No abstract available. |
| 22289993 | Result | Woyach JA, Lozanski G, Ruppert AS, Lozanski A, Blum KA, Jones JA, Flynn JM, Johnson AJ, Grever MR, Heerema NA, Byrd JC. Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features. Leukemia. 2012 Jun;26(6):1442-4. doi: 10.1038/leu.2011.375. Epub 2012 Jan 13. No abstract available. |
| 25596730 | Derived | Yeh YY, Chen R, Hessler J, Mahoney E, Lehman AM, Heerema NA, Grever MR, Plunkett W, Byrd JC, Johnson AJ. Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the acquired resistance to cyclin-dependent kinase inhibitors in leukemia. Oncotarget. 2015 Feb 20;6(5):2667-79. doi: 10.18632/oncotarget.2096. |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Overall Response Rate (CR + PR) | CR requires all of the following: Absence of lymphadenopathy in excess of 1 cm on physical exam; No hepatomegaly or splenomegaly on physical exam; Absence of constitutional symptoms; Normal CBC as exhibited by polymorphonuclear leukocytes > 1500/µL, platelets > 100,000/µL, hemoglobin > 11.0 g/dl (untransfused); lymphocyte count < 5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with < 30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. Patients with CR after induction but wih treatment-related persistent cytopenia is a PR. PR requires a > 50% decrease in peripheral lymphocyte count from pretreatment value, > 50% reduction in lymphadenopathy, and/or > 50% reduction in splenomegaly/hepatomegaly. These patients must have one of the following: polymorphonuclear leukocytes > 1,500/μL , platelets > 100,000/μL, hemoglobin > 11.0 g/dl (untransfused) or any with 50% improvement from pretreatment value. | Schedule was amended (cycle length) from 42 to 28 days, reduction in the number of doses per cycle from 4 to 3 and administration of prophylactic dexamethasone 20 mg IV on each treatment day. | Posted | Number | 95% Confidence Interval | percent of patients | Up to 8 months |
|
|
|
| Primary | Response Duration | Response evaluation criteria based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response. Descriptive statistics will be computed (median, range, mean, standard deviation, minimum, and maximum) on response duration. | Duration of response was not collected for patients. | Posted | Up to 8 months |
|
|
| Primary | Progression-free Survival (PFS) for Responding Patients as Assessed Using Standard Kaplan-Meier Methods | PFS was calculated from the date of study entry until time of disease progression or death, whichever came first, censoring patients alive and relapse free at last follow up. Patients who withdrew from study to undergo an allogeneic SCT (Stem cell transplantation) were censored at the time of transplantation. | Posted | Median | 95% Confidence Interval | months | Up to 5 years |
|
|
|
| Primary | Progression-free Survival for All Patients as Assessed Using Standard Kaplan-Meier Methods | PFS was calculated from the date of study entry until time of disease progression or death, whichever came first, censoring patients alive and relapse free at last follow up. Patients who withdrew from study to undergo an allogeneic SCT were censored at the time of transplantation. | Posted | Median | 95% Confidence Interval | months | Up to 5 years |
|
|
|
| Primary | Overall Survival | Overall survival data will be reported on a 3-month basis for 5 years | Posted | Median | 95% Confidence Interval | months | Up to 5 years |
|
|
|
| Primary | Toxicity | Toxicity determination based on NCI Common Toxicity Criteria version 3 and modified NCI Common toxicity guidelines for evaluating hematologic toxicity in leukemia. | Grade 3 to 4 infections requiring IV antibiotics and were generally related to upper or lower respiratory infections or infections of indwelling central venous catheters. | Posted | Number | percentage of patients | Measurement prior to each infusion, at end of therapy, 2 months post-completion and post-treatment follow-up every 3 months for two years. |
|
|
|
| Secondary | Pharmacokinetics (PK) (AUC) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol | Pharmacokinetics were performed on day 1 and day 8 of cycle 1 by plasma levels of both flavopiridol and metabolites of flavopiridol using Area Under the Curve (AUC) | The values are overall averages for all patients on days 1 and 8 - therefore, there is only a single value for each parameter. | Posted | Mean | Standard Deviation | μM*hr | During treatment day 1 and day 8 of cycle 1 |
|
|
|
| Secondary | PK (Cmax) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol | Pharmacokinetics were performed on day 1 and day 8 of cycle 1 by plasma levels of both flavopiridol and metabolites of flavopiridol | The values are overall averages for all patients on days 1 and 8 - therefore, there is only a single value for each parameter. | Posted | Mean | Standard Deviation | μM | During treatment day 1 and day 8 of course 1 |
|
|
|
| Secondary | PK as Assessed by Levels of Both Flavopiridol and Metabolites of Flavopiridol in Urine Samples | urine samples were collected in some patients during the first 24 hours after the start of the infusion on cycle 1, day 1 to isolate metabolites of flavopiridol to be used as internal standard for plasma metabolite quantification experiments. | Data for this PK analysis was not collected and analyzed. | Posted | Urine collected at 4 separate times in some patients during the first 24 hours after start of infusion on day 1 of course 1. |
|
|
| Secondary | Serial Levels of IL-6 as Assessed by Blood Plasma | IL-6 measures were adjusted for baseline values | IL-6 expression analysis was available for only day 1 and not day 8. | Posted | Mean | 95% Confidence Interval | pg/ml | 4.5 hours, 8 hours, 12 hours, and 24 hours following the initiation of therapy during day 1 of course 1 |
|
|
|
| Secondary | Comparison of CLL Cell Samples Taken at Registration/Diagnosis to CLL Cell Samples Taken at Time of Relapse | Samples will be examined for ex vivo sensitivity to flavopiridol, expression of select anti-apoptosis proteins, BCRP mRNA and protein expression, difference in gene expression by cDNA microarray and potentially by epigenetic arrays. Comparisons will be used to evaluate mechanisms of acquired flavopiridol resistance. | Data for this outcome as not collected and analyzed | Posted | At baseline and at time of relapse or when patient goes off therapy due to disease progression |
|
|
| Secondary | Correlation of Adverse Prognostic Factors With Response to Flavopiridol Treatment as Assessed by Interphase Cytogenetics, VH Mutational Status, ZAP-70 Protein Expression, CD38, and p53 | overall response rates (CR+PR) | Data were not collected and analyzed for VH mutational status, ZAP-70 protein expression, CD38, and p53 | Posted | Number | percentage of patients in each subgroup | up to 8 months |
|
|
|
| Secondary | Levels of Mcl-1 mRNA, Mcl-1 Protein, HIF-1alpha Protein, HIF-1alpha mRNA, NF-kappaB Activation, Total IkB, IkB Phosphorylation, GSK-beta Activity, and IL-6 Target Genes (i.e., STAT3) | Assessed by real time RT-PCR (mcl-1, HIF-1alpha), immunoblot analysis (mcl-1, HIF-1alpha, I-kappaB, I-kappaB phosphorylation, targets of IL-6), and electrophoretic mobility shift analysis (NF-kappaB activation) | Data was not collected and analyzed for this outcome | Posted | At baseline, 4.5 hours (end of continuous infusion), 8 hours, and approximately 24 hours following initiation of therapy |
|
|
| Secondary | Comparison of Clinical Response and Tumor Lysis in Vivo With Drug-induced Apoptosis and Mitochondrial Perturbation in Vitro as Assessed by Flow Cytometry | CLL cells will be incubated with control or flavopiridol (1 or 2.8 microMolar) for 4-hours followed by a 20 hours in media with 10% heat-inactivated human serum. Assessment of apoptosis following exposure of human CLL cells will be performed using annexin/PI flow cytometry. Patient samples with greater than 50% live cells (annexin-/PI-) following exposure to 2.8 microMolar flavopiridol will be considered to have insensitive disease. Patients whose CLL cells have less than 50% live cells at 1 microMolar will be considered to have highly sensitive disease. | A subset of patients who had sufficient material were analyzed according to response only. | Posted | Mean | Standard Deviation | percentage of priming cells | At baseline |
|
|
|
| 4 |
| 64 |
| 64 |
| 64 |
|
| Anemia | Blood and lymphatic system disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Thrombocytopenia | Injury, poisoning and procedural complications | CTCAE Version 3.0 | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Nausea and Vomiting | Gastrointestinal disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Anxiety/Depression | Psychiatric disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Tumor Lysis Syndrome | Metabolism and nutrition disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Cytokine Release Syndrome | Immune system disorders | CTCAE Version 3.0 | Systematic Assessment |
|
| Transaminitis | Investigations | CTCAE Version 3.0 | Systematic Assessment |
|
| Hyperbilirubinemia | Investigations | CTCAE Version 3.0 | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE Version 3.0 | Systematic Assessment |
|
Not provided
| D009369 |
| Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| 12 hours |
|
| 24 hours |
|