NCT00112723 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2016-08-08

This phase I/II trial is studying the side effects and best dose of flavopiridol and to see how well it works in treating patients with lymphoma or multiple myeloma. 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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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)

→

outcome · POSTED

Maximum Tolerated Dose (MTD)

→

outcome · POSTED

Complete and Partial Response Rate (Phase II)

→

outcome · POSTED

Qualitative and Quantitative Toxicities in Regard to Organ Specificity

→

outcome · POSTED

Lymphoid/Plasma Cell Malignancies

→

outcome · POSTED

Pharmacokinetics (Area Under the Curve; AUC) of Flavopiridol

→

outcome · POSTED

Number of Patients Reporting Acute Infusion Toxicity (e.g., Fever, Hypotension, Tumor Pain, and Dyspnea)

→

outcome · POSTED

Induced Response in Patients Independent of p53 Mutational Status

→

outcome · POSTED

Pharmacodynamic Effects of Flavopiridol on Normal Peripheral Blood Mononuclear Cells (PBMCs).

→

outcome · POSTED

Pharmacokinetics (Cmax) of Flavopiridol

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Diagnosis of 1 of the following hematologic malignancies: * Hodgkin's lymphoma * Non-Hodgkin's lymphoma (NHL) * Multiple myeloma * Patients in the phase II portion of the study are enrolled in 1 of the following strata according to diagnosis\* * Stratum 1: Indolent B-cell NHL (non-Hodgkin's lymphoma), follicle center B-cell NHL (grade 1, 2, or 3), marginal zone lymphoma, Waldenstrom's macroglobulinemia, or small lymphocytic lymphoma (without blood lymphocytosis at any point in the disease process) * Must have progressive lymphadenopathy, worsening cytopenias, or progressive symptoms attributed to lymphoma * Must require therapy, as determined by progressive anemia, thrombocytopenia, symptoms (e.g., fever, night sweats, weight loss, or fatigue), or progressive lymphadenopathy that causes discomfort * Received ≥ 2 prior therapies, including rituximab * Stratum 1a: Hairy cell leukemia * Must require therapy, as determined by progressive cytopenias or symptoms (fever, night sweats, weight loss, or fatigue) * Must have received ≥ 2 therapies * Stratum 2: Mantle cell lymphoma, as determined by the presence of cyclin D1 staining OR t(11;14) * Stratum 3: Intermediate grade B-cell NHL, including diffuse large B-cell NHL and T-cell rich B-cell NHL * Diffuse large B-cell NHL arising from an indolent NHL (i.e., transformed lymphoma) allowed * Ineligible for potentially curative autologous stem cell transplantation * Stratum 4: T-cell and natural killer-cell NHL, including anaplastic large cell lymphoma and peripheral T-cell NHL * Primary cutaneous lymphoma or Sezary syndrome allowed provided criteria for measurable disease are met * Received ≥ 1 prior systemic therapy * Stratum 5: Hodgkin's lymphoma * Any of the following subtypes are allowed: * Nodular sclerosing * Mixed cellularity * Lymphocyte predominant * Lymphocyte depleted * Ineligible for potentially curative autologous stem cell transplantation * Stratum 6: Progressive stage I or stage II or IIIA multiple myeloma meeting ≥ 1 major and 1 minor criterion OR ≥ 3 minor criteria as follows: * Major criteria * Plasmacytoma on tissue biopsy * Bone marrow plasmacytosis ≥ 30% of marrow cellularity * Monoclonal paraprotein ≥ 3,500 mg/dL (IgG), or ≥ 2,000 mg/dL (IgA), OR monoclonal protein (Bence-Jones protein) ≥ 1,000 mg by 24-hour urine collection * Minor criteria * Bone marrow plasmacytosis 10-29% of marrow cellularity * Monoclonal paraprotein \< 3,500 mg/dL (IgG) or \< 2,000 mg/dL (IgA) * Lytic bone lesions by x-ray or CT scan * Decrease in normal IgM (\< 50 mg/dL), IgA (\< 100 mg/dL), or IgG (\< 600 mg/dL) * Relapsed or refractory disease * Measurable disease, defined by 1 of the following: * At least 1 node \> 2 cm by CT scan * Measurable disease in a lymphoid structure (i.e., spleen) by CT scan * Bone marrow involvement (\> 20% of marrow cellularity) * Patients with multiple myeloma must have detectable serum or urinary paraprotein * Patients with only cutaneous or subcutaneous disease (i.e., no measurable lymph node or bone marrow disease) are eligible if the extent of rash or skin involvement OR the size of the nodules are measurable * Must have received ≥ 1 prior therapy * Steroids alone are not considered prior therapy for patients with NHL or Hodgkin's lymphoma * High-dose dexamethasone is considered 1 prior therapy for patients with multiple myeloma * No standard effective therapy exists * No HIV-associated lymphoma * No nonsecretory multiple myeloma * Performance status - ECOG (Eastern Cooperative Oncology Group) 0-2 * No concurrent hormonal therapy except steroids for new adrenal failure or hormones administered for non-disease-related conditions (e.g., insulin for diabetes) * Hemoglobin ≥ 9.0 g/dL\* * Absolute neutrophil count ≥ 1,500/mm\^3\* * Platelet count ≥ 50,000/mm\^3\* * AST (aspartate aminotransferase) ≤ 3 times upper limit of normal (ULN) * Bilirubin ≤ 2 times ULN * No major renal dysfunction that would preclude study compliance or participation * Phase I: * Creatinine ≤ 1.5 mg/dL * Creatinine clearance ≥ 70 mL/min * Phase II: * Creatinine ≤ 2.0 mg/dL * Creatinine clearance ≥ 50 mL/min * No cardiac or vascular dysfunction that would preclude central venous access, vigorous hydration, or hemodialysis * No other major cardiac dysfunction that would preclude study compliance or participation * No major pulmonary dysfunction that would preclude study compliance or participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) that would preclude study compliance or participation * No other major organ system (including neurological or psychiatric) dysfunction that would preclude study compliance or participation * Prior radiotherapy, including radioimmunotherapy, allowed * No concurrent radiotherapy * Prior idiotype vaccination or stem cell transplantation allowed * More than 6 weeks since prior mitomycin or nitrosoureas * No other concurrent chemotherapy * More than 4 weeks since other prior therapy * Prior systemic steroids allowed
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: alvocidib
label
Treatment (alvocidib)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (alvocidib)
description
Given IV
name
alvocidib
other Names
FLAVO
flavopiridol
HMR 1275
L-868275
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 46
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
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)
time Frame
28 days
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.
measure
Maximum Tolerated Dose (MTD)
time Frame
28 days
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.
measure
Complete and Partial Response Rate (Phase II)
time Frame
Up to 2 years
description
The NCI Common Toxicity Criteria for Adverse Events (version 3.0) were used to define and grade toxicity for patients.
measure
Qualitative and Quantitative Toxicities in Regard to Organ Specificity
time Frame
Up to 30 days after completion of study treatment
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.
measure
Lymphoid/Plasma Cell Malignancies
time Frame
Up to 2 years

secondary Outcomes

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.
measure
Pharmacokinetics (Area Under the Curve; AUC) of Flavopiridol
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
measure
Number of Patients Reporting Acute Infusion Toxicity (e.g., Fever, Hypotension, Tumor Pain, and Dyspnea)
time Frame
Up to 30 days after completion of study treatment
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.
measure
Induced Response in Patients Independent of p53 Mutational Status
time Frame
Up to 2 years
description
The correlation of the pharmacodynamic effects of flavopiridol on normal peripheral blood mononuclear cells (PBMCs)
measure
Pharmacodynamic Effects of Flavopiridol on Normal Peripheral Blood Mononuclear Cells (PBMCs).
time Frame
Day 1
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.
measure
Pharmacokinetics (Cmax) of Flavopiridol
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

Full study description

brief Summary: This phase I/II trial is studying the side effects and best dose of flavopiridol and to see how well it works in treating patients with lymphoma or multiple myeloma. 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.
detailed Description: PRIMARY OBJECTIVES: I. Determine the disease-specific dose-limiting toxicity and maximum tolerated dose of flavopiridol in patients with relapsed or refractory lymphoma or multiple myeloma. II. Determine the complete and partial response rate in patients with selected non-Hodgkin's lymphoma (e.g., indolent B-cell, mantle cell, intermediate grade B-cell, and T/NK-cell), Hodgkin's lymphoma, or multiple myeloma treated with this drug. III. Determine the qualitative and quantitative toxic effects or this drug, in terms of organ specificity, time course, predictability, and reversibility in these patients. IV. Determine subsets of lymphoid/plasma cell malignancies that are suitable for larger phase II studies designed to further evaluate the efficacy and toxicity of this drug in these patients. SECONDARY OBJECTIVES: I. Determine the pharmacokinetics of this drug in these patients. II. Determine the effect of this drug on innate immunity (including T-, B-, and NK-cell subsets) and quantitative immunoglobulin levels in these patients. III. Determine whether acute infusion toxicity (e.g., fever, hypotension, tumor pain, and dyspnea) observed with other flavopiridol treatment schedules is related to a cytokine-release syndrome in these patients. IV. Determine whether this drug induces response (independent of p53 mutational status) in these patients. OUTLINE: This is a phase I, dose-escalation study followed by a multicenter, phase II, pilot study. Patients enrolled in the phase II portion of the study are stratified according to diagnosis. 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. NOTE: The phase II treatment dose and schedule for hairy cell leukemia patients will be adapted from that developed in previous phase II studies of flavopiridol for the treatment of chronic lymphocytic leukemia. After completion of study therapy, patients are followed every 3 months for 2 years.

Source references

references

citation
Hofmeister CC, Poi M, Bowers MA, Zhao W, Phelps MA, Benson DM, Kraut EH, Farag S, Efebera YA, Sexton J, Lin TS, Grever M, Byrd JC. A phase I trial of flavopiridol in relapsed multiple myeloma. Cancer Chemother Pharmacol. 2014 Feb;73(2):249-57. doi: 10.1007/s00280-013-2347-y. Epub 2013 Nov 16.
pmid
24241210
type
DERIVED

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-206dfcdf8fab0fc52e51
requested nct id
NCT00112723
primary nct id
NCT00112723
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
payload sha256
52b4faa8fc497b61e76b16e5d84f90629c8d74b2a803cd325e7e5691704ced9b
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-206dfcdf8fab0fc52e51
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT00112723
occurrences
context exact
NCT00112723
end
11
exact text
NCT00112723
start
0
offset unit
unicode_code_points
query cond
Plasma Cell Neoplasms
query disease state id
ds-plasma-cell-neoplasms
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
source json pointer
/studies/17/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
eb830069a847e852b4c49a22cadecc02a316948dca244113655f8dad07fa09aa
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice