Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Neoplasms

Immune System Diseases

Rare Diseases

Thrombocytopenia

Recurrence

Lymphoma

Leukemia

Leukemia, Lymphoid

Anemia

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Prolymphocytic

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Blood Platelet Disorders

Cytopenia

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Lenalidomide

Alvocidib

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive alvocidib IV over 4.5 hours on days 1, 8, and 15 in course 1 followed by a week of rest. Beginning in course 2 and all subsequent courses, patients receive lenalidomide PO QD on days 1-21 and alvocidib IV over 4.5 hours on days 3, 10, and 17. Treatment repeats every 35 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Alvocidib Hydrochloride

Pharmacological Study

Laboratory Biomarker Analysis

Kristie Blum

This phase I trial studies the side effects and best dose of lenalidomide when given together with alvocidib in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Lenalidomide may stop the growth of leukemia or lymphoma by blocking blood flow to the cancer. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with alvocidib may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of flavopiridol (alvocidib) in combination with lenalidomide in patients with relapsed or refractory B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

II. To define the specific toxicities and the dose limiting toxicity (DLT) of flavopiridol in combination with lenalidomide in the treatment of patients with relapsed or refractory CLL/SLL.

SECONDARY OBJECTIVES:

I. To assess preliminary efficacy of flavopiridol combined with lenalidomide in patients with relapsed/refractory CLL/SLL to justify future, rigorous phase II studies of the combination in CLL.

II. To determine the pharmacokinetics of flavopiridol and lenalidomide alone and in combination in patients with CLL/SLL.

III. To correlate select pre-treatment prognostic markers, including interphase cytogenetics with minimal residual disease, progression-free survival, response, and toxicity following combination therapy with flavopiridol and lenalidomide.

IV. To determine patient cytokine expression profiles immediately pre-treatment, after flavopiridol dosing, and after combination flavopiridol and lenalidomide therapy to assess the impact of lenalidomide on flavopiridol induced cytokine release (interleukin \[IL\]-6).

V. To assess if pre-treatment ex vivo and in vivo (day 1 and day 3 of lenalidomide) immune (B-cell, natural killer \[NK\] cell, and T-cell) activation correlates with response and toxicity of lenalidomide therapy.

VI. To assess the in vivo effect of lenalidomide on flavopiridol on the modulation of selected intracellular pharmacodynamic targets including signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3), myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1), and other downstream IL-6 targets.

OUTLINE: This is a dose-escalation study of lenalidomide.

Patients receive alvocidib intravenously (IV) over 4.5 hours on days 1, 8, and 15 in course 1 followed by a week of rest. Beginning in course 2 and all subsequent courses, patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 and alvocidib IV over 4.5 hours on days 3, 10, and 17. Treatment repeats every 35 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Lenalidomide and Alvocidib in Treating Patients With Relapsed or Refractory B-cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Phase 1 Trial of Flavopiridol in Combination With Lenalidomide in Patients With Relapsed or Refractory B-Cell CLL/SLL

Toxicities classified as DLT during course 1 will not be considered DLT for the combination of lenalidomide and flavopiridol, but will result in patient removal from the study.

Samples will be analyzed in batches to assess plasma drug concentrations, the plasma drug concentration-time profile (AUC), volume of distribution (Vss), clearance (CL), and half-life. Standard paired statistical tests, parametric and nonparametric, will be used to compare baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

Standard paired statistical tests, parametric and nonparametric, will be used to compare baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

National Cancer Institute (NCI)

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Venetoclax

Azacitidine

Decitabine

Antimetabolites

INDUCTION: Patients receive decitabine IV over 1 hour on days 1-10, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10, or 1-14, and venetoclax PO QD on days 1-14 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive decitabine IV over 1 hour on days 1-5, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10 or 1-14, and venetoclax PO QD on days 1-10. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Yesid Alvarado-Valero

This phase I/II trial investigates the side effects and best dose of alvocidib when given together with decitabine and venetoclax and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed), has not responded to previous treatment (refractory), or as frontline treatment for patients unable to receive other therapies (unfit). Alvocidib, decitabine, and venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the safety of alvocidib hydrochloride (alvocidib) in combination with decitabine and venetoclax in relapsed or refractory patients with acute myeloid leukemia (AML) or as frontline therapy in unfit/frail patients with AML. (Phase I) II. To determine the efficacy alvocidib in combination with decitabine and venetoclax in relapsed or refractory patients with acute myeloid leukemia (AML) or as frontline therapy in unfit/frail patients with AML. (Phase II)

SECONDARY OBJECTIVE:

I. To determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables, including overall survival (OS), event-free survival (EFS) and duration of response (DOR) of patients treated with this combination.

EXPLORATORY OBJECTIVES:

I. To determine the minimal residual disease (MRD) after treatment with this combination and its impact in long-term outcome.

II. To determine the effect of the level of pre-treatment expression of BCL-2 and MCL-1 (by BH3 profiling) with response to this combination.

III. To determine the effect of this treatment combination on responding patients transitioning to hematopoietic stem cell transplantation (HSCT).

OUTLINE: This is a phase I, dose-escalation study of alvocidib followed by a phase II study.

INDUCTION: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10, or 1-14, and venetoclax orally (PO) once daily (QD) on days 1-14 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive decitabine IV over 1 hour on days 1-5, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10 or 1-14, and venetoclax PO QD on days 1-10. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks.

Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML

A Phase 1/2 Study of Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML

Measured using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Will estimate the response rate for the combination treatment, along with the 95% credible interval.

The duration of response is defined as the number of days from the date of initial response (partial response \[PR\] or better) to the date of first documented disease progression/relapse or death, whichever occurs first.

Event-free survival is defined as the number of days from the date of treatment initiation (e.g., cycle 1 day 1 \[C1D1\]) to the date of documented treatment failure, relapses from complete response (CR), or death from any cause, whichever occurs first, and will be calculated for all patients. Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

M.D. Anderson Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Testicular Neoplasms

Seminoma

Neoplasms, Germ Cell and Embryonal

Germinoma

Ovarian Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Genital Neoplasms, Male

Genital Diseases, Male

Male Urogenital Diseases

Testicular Diseases

Germ Cells Tumors

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Testicular Seminoma

Nonseminomatous Germ Cell Tumor

Extragonadal Germ Cell Tumor

Central Nervous System Germinoma

Ovarian Cancer

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Folic Acid

Calcium, Dietary

Vitamin B Complex

Hormones

Immunosuppressive Agents

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Patients receive alvocidib IV over 1 hour and oxaliplatin IV over 2 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Patients receive alvocidib IV over 1 hour, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Leucovorin Calcium

Darren Feldman

This phase II trial is studying alvocidib and oxaliplatin to see how well they work when given with or without fluorouracil and leucovorin calcium in treating patients with relapsed or refractory germ cell tumors. Drugs used in chemotherapy, such as alvocidib, oxaliplatin, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving alvocidib together with oxaliplatin with or without fluorouracil and leucovorin calcium may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To evaluate the antitumor efficacy of the combination of flavopiridol and oxaliplatin with or without 5-FU and leucovorin in patients with relapsed or refractory GCT. The necessity of 5-FU and leucovorin to the combination will also be indirectly tested in this study.

SECONDARY OBJECTIVES:

I. To further evaluate the safety of flavopiridol in combination with oxaliplatin with or without 5-fluorouracil and leucovorin in patients with refractory or relapsed GCT.

II. To evaluate the time to tumor response (TTR) and progression-free survival for patients with refractory or relapsed GCT treated with flavopiridol in combination with oxaliplatin with or without 5-fluorouracil and leucovorin.

III. To explore the association between treatment response and p21, p53 and apoptotic markers.

OUTLINE: Patients are initially enrolled in part A (closed to accrual as of 11/15/2010). Depending on response to treatment, additional patients may be enrolled in part B.

PART A (alvocidib and oxaliplatin) (closed to accrual as of 11/15/2010): Patients receive alvocidib IV over 1 hour and oxaliplatin IV over 2 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

PART B (alvocidib and FOLFOX): Patients receive alvocidib IV over 1 hour, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Tumor tissue samples may be collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up every 4-8 weeks.

Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

A Non-randomized Phase 2 Study of Alvocidib (Flavopiridol) Plus Oxaliplatin With or Without 5-FU and Leucovorin for Relapsed or Refractory Germ-Cell Tumors

graded using the NCI CTCAE version 4.0.See adverse event section

Number of Participants with Partial Response (PR), Stable Disease (SD), Progression of Disease (POD) Per Response Evaluation Criteria In Solid Tumors Criteria" (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Part A (Alvocidib and Oxaliplatin)

Part B (Alvocidib and FOLFOX)

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Dr. Darren Feldman

Partial Response

Stable Disease

Progression of Disease

Objective Response Rate

Toxicity

Progression-free Survival

Time to Tumor Response

6 weeks: Flavopiridol: 70 mg/m2/day IV over 1 hr on days 1, 15 and 29. Oxaliplatin: 85 mg/m2/day IV over 2 hrs on days 1, 15 and 29.

Part A

6 wks: Flavopiridol:70 mg/m2/day IV 1 hr Days 1, 15 \& 29. Oxaliplatin:85 mg/m2/day IV 2 hrs Days 1, 15 \& 29. Leucovorin:400 mg/m2/day IV 2 hrs Days 1, 15 \& 29.

5-FU: 400 mg/m2 IV 15 min, and 1800 mg/m2 IV 48 hrs Days 1-2, 15-16 \& 29-30.

Part B

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, Non-Hodgkin

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Bortezomib

Patients receive bortezomib IV over 3-5 seconds followed by flavopiridol IV over 1 hour on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Steven Grant

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may increase the effectiveness of flavopiridol by making cancer cells more sensitive to the drug. Giving bortezomib together with flavopiridol may kill more cancer cells. This phase I trial is studying the side effects and best dose of bortezomib and flavopiridol in treating patients with recurrent or refractory indolent B-cell neoplasms.

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose of bortezomib and flavopiridol in patients with recurrent or refractory indolent B-cell neoplasms.

SECONDARY OBJECTIVES:

I. To determine the toxic effects and maximum tolerated dose of this regimen in these patients.

II. To determine disease-related effects of this regimen in these patients. III. To determine the pharmacodynamics of this regimen in patients with myeloma.

IV. To determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive bortezomib IV over 3-5 seconds followed by flavopiridol IV over 1 hour on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Bortezomib and Flavopiridol in Treating Patients With Recurrent or Refractory Indolent B-Cell Neoplasms

Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol NSC 649890) in Patients With Recurrent or Refractory Indolent B-Cell Neoplasms

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Rituximab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).

Diagnostic Laboratory Biomarker Analysis

Joseph Flynn

This phase I trial is studying the side effects and the best dose of alvocidib when given together with cyclophosphamide and rituximab in treating patients with high risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Other find cancer cells and help kill them or carry cancer-killing substances to them. Giving cyclophosphamide, alvocidib, and rituximab together may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the dose-limiting toxicity and maximum-tolerated dose of treatment with cyclophosphamide, alvocidib, and rituximab in patients with high-risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

II. To determine the feasibility of administering this regimen as an outpatient regimen in these patients.

SECONDARY OBJECTIVES:

I. To determine the complete response rate, partial response rate, and minimal-residual disease-negative response rate in patients treated with this regimen.

II. To determine the pharmacokinetics of alvocidib and dexamethasone as part of this regimen.

III. To determine the immunologic effects of this regimen as measured by serial T-cell and NK-cell number, T-cell function, and immunoglobulin levels.

OUTLINE: This is a dose-escalation study of alvocidib.

Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies.

After completion of study treatment, patients are followed up for up to 5 years.

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL

Determined using the CTEP Active Version of the CTCAE.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lenalidomide and Alvocidib in Treating Patients With Relapsed or Refractory B-cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma	NCT00735930	Anemia Chronic Lymphoc... Prolymphocytic ... Recurrent Small... Refractory Chro... Thrombocytopeni...	Alvocidib Hydro... Lenalidomide Pharmacological... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML	NCT04493099	Recurrent Acute... Refractory Acut...	Alvocidib Hydro... Decitabine Venetoclax	18 Years -	M.D. Anderson Cancer Center
Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors	NCT00957905	Recurrent Extra... Recurrent Malig... Recurrent Malig... Recurrent Malig... Recurrent Ovari... Stage III Testi... Stage IV Extrag... Stage IV Extrag... Stage IV Ovaria...	Alvocidib Hydro... Fluorouracil Leucovorin Calc... Oxaliplatin	18 Years -	National Cancer Institute (NCI)
Bortezomib and Flavopiridol in Treating Patients With Recurrent or Refractory Indolent B-Cell Neoplasms	NCT00082784	Extranodal Marg... Nodal Marginal ... Recurrent Adult... Recurrent Adult... Recurrent Adult... Recurrent Grade... Recurrent Grade... Recurrent Grade... Recurrent Mantl... Recurrent Margi... Refractory Plas... Splenic Margina... Waldenstrom Mac...	Bortezomib Alvocidib Hydro... Pharmacological...	18 Years -	National Cancer Institute (NCI)
Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma	NCT01076556	Chronic Lymphoc... Prolymphocytic ... Recurrent Small... Refractory Chro... Stage I Chronic... Stage I Small L... Stage II Chroni... Stage II Small ... Stage III Chron... Stage III Small... Stage IV Chroni... Stage IV Small ...	Alvocidib Hydro... Cyclophosphamid... Diagnostic Labo... Pharmacological... Rituximab	18 Years -	National Cancer Institute (NCI)
Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors	NCT00957905	Recurrent Extra... Recurrent Malig... Recurrent Malig... Recurrent Malig... Recurrent Ovari... Stage III Testi... Stage IV Extrag... Stage IV Extrag... Stage IV Ovaria...	Alvocidib Hydro... Fluorouracil Leucovorin Calc... Oxaliplatin	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for alvocidib hydrochloride