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Trial record 82 of 179 for:    "Lymphomatoid Granulomatosis"

Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00112723
Recruitment Status : Terminated (Administratively Complete)
First Posted : June 3, 2005
Results First Posted : August 8, 2016
Last Update Posted : August 8, 2016
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Lymphocyte Depletion Hodgkin Lymphoma
Adult Lymphocyte Predominant Hodgkin Lymphoma
Adult Mixed Cellularity Hodgkin Lymphoma
Adult Nodular Sclerosis Hodgkin Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Multiple Myeloma
Splenic Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Waldenström Macroglobulinemia
Intervention Drug: alvocidib
Enrollment 46
Recruitment Details Patients were accrued to the study between April 2006 and September 2010.
Pre-assignment Details Patients with confirmed diagnosis of NHL (Non-Hodgkin's lymphoma) were accrued to one of the four cohorts defined by the World Health Organization criteria: indolent B-cell, mantle cell, intermediate-grade B-cell including transformed lymphoma and T-/NK-cell excluding primary cutaneous disease.
Arm/Group Title Dose Level 1 (Flavopiridol 30 mg/m2 + 30 mg/m2) Dose Level 2 (Flavopiridol 30 mg/m2 + 50 mg/m2) Dose Level 3 (Flavopiridol 50 mg/m2 + 50 mg/m2)
Hide Arm/Group Description Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 13 19 14
Patients Evaluable for Toxicity 11 12 12
Completed 11 12 12
Not Completed 2 7 2
Arm/Group Title Treatment (Alvocidib)
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PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

Overall Number of Baseline Participants 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 46 participants
66
(34 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
Female
20
  43.5%
Male
26
  56.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Patients
Number Analyzed 46 participants
United States 45
Canada 1
Eastern Cooperative Oncology Group (ECOG) Performance status  
Measure Type: Number
Unit of measure:  Patients
Number Analyzed 46 participants
0 (Fully active) 8
1 (Restricted in physically strenuous activity) 34
2 (Ambulatory capable of all selfcare) 4
Diagnosis  
Measure Type: Number
Unit of measure:  Patients
Number Analyzed 46 participants
Indolent B-cell 15
intermediate grade B-NHL 17
Mantle cell lymphoma 7
T/NK cell NHL 7
1.Primary Outcome
Title Disease-specific Dose-limiting Toxicity and Maximum Tolerated Dose of Flavopiridol Graded According to the CTCAE (Common Toxicity Criteria for Adverse Effects) Version 4.0 (Phase I)
Hide Description Dose limiting toxicity (DLT) for an individual disease group is defined as 1) any grade 3-4 non-hematologic toxicity (except leukopenia or neutropenia) that does not resolve or decrease to grade 1-2 within 2 weeks, or 2) any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1 (Flavopiridol 30 mg/m2 + 30 mg/m2) Dose Level 2 (Flavopiridol 30 mg/m2 + 50 mg/m2) Dose Level 3 (Flavopiridol 50 mg/m2 + 50 mg/m2)
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

Overall Number of Participants Analyzed 11 19 14
Measure Type: Number
Unit of Measure: patients
0 0 0
2.Primary Outcome
Title Maximum Tolerated Dose (MTD)
Hide Description The maximum tolerated dose (MTD) is defined as that dose level beneath the dose at which 2 or more of 6 patients experience DLT.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1 (30+30) Level 2 (30+50) Level 3 (50+50)
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

Overall Number of Participants Analyzed 11 12 12
Measure Type: Number
Unit of Measure: mg/m2
60 80 100
3.Primary Outcome
Title Complete and Partial Response Rate (Phase II)
Hide Description Patients were assessed for clinical response after two , four and six cycle with laboratory studies, physical exam, and CT scans. Response was evaluated using the modified NCI-sponsored Working Group Lymphoma Response Criteria.
Time Frame Up to 2 years
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Hide Analysis Population Description
Includes patients enrolled with Indolent B-cell NHL, Intermediate Grade B NHL, Mantle cell NHL and T/NK-cell NHL
Arm/Group Title Dose Level 1 (Flavopiridol 30 mg/m2 + 30 mg/m2) Dose Level 2 (Flavopiridol 30 mg/m2 + 50 mg/m2) Dose Level 3 Dose (Flavopiridol 50 mg/m2 + 50 mg/m2)
Hide Arm/Group Description:
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Overall Number of Participants Analyzed 12 17 14
Measure Type: Number
Unit of Measure: patients
Complete Response 0 0 0
Partial Response 2 2 2
4.Primary Outcome
Title Qualitative and Quantitative Toxicities in Regard to Organ Specificity
Hide Description The NCI Common Toxicity Criteria for Adverse Events (version 3.0) were used to define and grade toxicity for patients.
Time Frame Up to 30 days after completion of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Grade 3 and 4 toxicities.
Arm/Group Title Dose Levels 1, 2, 3
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Dose Level 1 (30 mg/m2 + 30 mg/m2), Dose Level 2 (30 mg/m2 + 50 mg/m2), Dose Level 3 (50 mg/m2 + 50 mg/m2)

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: percentage of patients
Leukopenia 86
Neutropenia 23
Infection 20
Diarrhea 51
Fatigue 34
5.Primary Outcome
Title Lymphoid/Plasma Cell Malignancies
Hide Description Identify subsets, based on levels of response (PR and SD), of lymphoid / plasma cell malignancies that are suitable for larger phase II studies designed to further evaluate the efficacy and toxicity of flavopiridol.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Response indicated for Indolent B-cell NHL, Mantle cell NHL and T-cell NHL
Arm/Group Title Cohort 1 Cohort 2 Cohort 4
Hide Arm/Group Description:
Patients diagnosed with Indolent B-cell NHL
Patients diagnosed with Mantle Cell NHL
Patients diagnosed with T Cell NHL
Overall Number of Participants Analyzed 13 6 6
Measure Type: Number
Unit of Measure: patients
Partial Response 3 2 0
Stable Disease 0 0 3
6.Secondary Outcome
Title Pharmacokinetics (Area Under the Curve; AUC) of Flavopiridol
Hide Description Whole blood samples were collected for pharmacokinetics analysis during the first (Day 1) and fourth (Day 22) treatments during cycle 1. Samples were collected on both occasions prior to dosing and at 0.5, 1, 3, 4.5, 6, 8 and 24 hour after the start of the bolus infusion.
Time Frame 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
total of 71 PK (Pharmacokinetic) profiles comprising 484 plasma concentration were determined for 45 of 46 patients following treatment
Arm/Group Title All Dose Levels of Alvocidib
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: hr×μM
Day 1 10.404  (5.923)
Day 22 11.949  (5.109)
7.Secondary Outcome
Title Number of Patients Reporting Acute Infusion Toxicity (e.g., Fever, Hypotension, Tumor Pain, and Dyspnea)
Hide Description [Not Specified]
Time Frame Up to 30 days after completion of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Dose Levels of Alvocidib
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: patients
8
8.Secondary Outcome
Title Induced Response in Patients Independent of p53 Mutational Status
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data not available due to studies were not conducted by collaborating laboratory Investigator
Arm/Group Title Dose Level 1 (Flavopiridol 30 mg/m2 + 30 mg/m2) Dose Level 2 (Flavopiridol 30 mg/m2 + 50 mg/m2) Dose Level 3 (Flavopiridol 50 mg/m2 + 50 mg/m2)
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Pharmacodynamic Effects of Flavopiridol on Normal Peripheral Blood Mononuclear Cells (PBMCs).
Hide Description The correlation of the pharmacodynamic effects of flavopiridol on normal peripheral blood mononuclear cells (PBMCs)
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data not available due to studies were not conducted by collaborating laboratory Investigator
Arm/Group Title Dose Level 1 (Flavopiridol 30 mg/m2 + 30 mg/m2) Dose Level 2 (Flavopiridol 30 mg/m2 + 50 mg/m2) Dose Level 3 (Flavopiridol 50 mg/m2 + 50 mg/m2)
Hide Arm/Group Description:
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Pharmacokinetics (Cmax) of Flavopiridol
Hide Description Whole blood samples were collected for pharmacokinetics analysis during the first (Day 1) and fourth (Day 22) treatments during cycle 1. Samples were collected on both occasions prior to dosing and at 0.5, 1, 3, 4.5, 6, 8 and 24 hour after the start of the bolus infusion.
Time Frame 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Dose Levels of Alvocidib
Hide Arm/Group Description:

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: μM
Day 1 1.954  (0.886)
Day 22 2.071  (0.820)
Time Frame Patients were assessed for clinical response after two, four and six cycles with laboratory studies, physical exam, and CT scans.
Adverse Event Reporting Description NCI Common Toxicity Criteria for Adverse Events (version 3.0) was used to define and grade toxicity.
 
Arm/Group Title Treatment (Alvocidib)
Hide Arm/Group Description

PHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive flavopiridol* as in phase I at the MTD determined in phase I.

alvocidib: Given IV

All-Cause Mortality
Treatment (Alvocidib)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Alvocidib)
Affected / at Risk (%) # Events
Total   0/35 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Alvocidib)
Affected / at Risk (%) # Events
Total   34/35 (97.14%)    
Blood and lymphatic system disorders   
Anemia  1  22/35 (62.86%)  22
Gastrointestinal disorders   
Nausea  1  12/35 (34.29%)  12
Vomiting  1  10/35 (28.57%)  10
Anorexia  1  8/35 (22.86%)  8
Diarrhea  1  27/35 (77.14%)  27
General disorders   
Neutropenia fever  1  4/35 (11.43%)  4
Fatigue  1  21/35 (60.00%)  21
Immune system disorders   
Cytokine Release Syndrome  1  8/35 (22.86%)  8
Infections and infestations   
Infection  1  9/35 (25.71%)  9
Injury, poisoning and procedural complications   
Thrombocytopenia  1  13/35 (37.14%)  13
Investigations   
Leukopenia  1  30/35 (85.71%)  30
Neutropenia  1  34/35 (97.14%)  34
Lymphopenia  1  25/35 (71.43%)  25
Increased ALT/AST  1  12/35 (34.29%)  12
Hyperbilirubinemia  1  6/35 (17.14%)  6
Metabolism and nutrition disorders   
Tumor Lysis Syndrome  1  8/35 (22.86%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE version 3.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Jeffrey Jones, MD
Organization: The Ohio State University Comprehensive Cancer Center
Phone: 614-293-3507
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112723     History of Changes
Other Study ID Numbers: NCI-2011-01346
NCI-2011-01346 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
OSU-04100
CDR0000429577
OSU-2005C0006
NCI-7002
OSU 04100 ( Other Identifier: Ohio State University Medical Center )
7002 ( Other Identifier: CTEP )
U01CA076576 ( U.S. NIH Grant/Contract )
N01CM00070 ( U.S. NIH Grant/Contract )
P30CA016058 ( U.S. NIH Grant/Contract )
First Submitted: June 2, 2005
First Posted: June 3, 2005
Results First Submitted: March 23, 2015
Results First Posted: August 8, 2016
Last Update Posted: August 8, 2016