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

NCT00735930 | Completed Phase 1

• 8 other identifiers: NCI-2009-00269OSU-080562008C0033CDR0000738866OSU 080568046P30CA016058U01CA076576
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• MTD of lenalidomide when combined with alvocidib, defined as the maximum dose level with fewer than 2 of 6 patients experiencing dose limiting toxicity (DLT)

  Up to day 70

• Incidence of DLT in patients treated with alvocidib and lenalidomide graded according to NCI CTCAE version 4.0

  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.

  Up to day 70

Secondary Outcomes (8)

• Pharmacokinetic parameters of alvocidib and lenalidomide alone and in combination in plasma samples

  Baseline, day 1 of course 1, and on days 2-3 of course 2

• Plasma IL-6 and selected cytokine levels

  Up to 5 years

• B-cell activation as assessed by surface antigen (CD40, CD80, CD86, HLA-DR, and CD95) expression

  Up to 5 years

• Intracellular pharmacodynamic targets including STAT3, Mcl-1, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)

  Up to 5 years

• Response assessed by National Cancer Institute-Sponsored Working Group guidelines

  Up to 5 years

Study Arms (1)

Treatment (alvocidib, lenalidomide)

EXPERIMENTAL

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.

Drug: Alvocidib Hydrochloride; Drug: Lenalidomide; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Alvocidib Hydrochloride DRUG

Given IV

Also known as: FLAVO, HL-275, HMR 1275

Treatment (alvocidib, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, IMiD-1

Treatment (alvocidib, lenalidomide)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (alvocidib, lenalidomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alvocidib, lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed B-cell CLL/SLL according to World Health Organization (WHO) criteria, or B-cell prolymphocytic leukemia (B-PLL) arising from CLL with at least one of the following indications for treatment:
• Progressive disease or marked splenomegaly and/or lymphadenopathy
• Anemia (hemoglobin \< 11 mg/dL) or thrombocytopenia (platelets \< 100,000/mm\^3)
• Unexplained weight loss exceeding 10% of body weight over the preceding 6 months
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grade 2 or 3 fatigue
• Fevers \> 100.5 or night sweats for greater than 2 weeks without evidence of infection
• Progressive lymphocytosis, with an increase exceeding 50% over a 2 month period or a doubling time of less than 6 months
• Must have at least one prior therapy that includes either fludarabine (or equivalent nucleoside analogue) or an alternative regimen if a contra-indication to fludarabine exists (i.e., autoimmune hemolytic anemia); prior therapy with flavopiridol is not permitted; prior lenalidomide is permitted provided that it has been \> 6 months since the last lenalidomide dose
• Eastern Cooperative Oncology Group (ECOG) performance status =\< (Karnofsky \>= 60%)
• White blood cell count =\< 150,000/mm\^3
• Absolute neutrophil count \>= 1,000/mm\^3
• Platelets \>= 30,000/mm\^3
• Total bilirubin =\< 1.5 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 X institutional ULN
• Creatinine =\< 1.5 mg/dL OR creatinine clearance \>= 60 ml/min

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Anemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Thrombocytopenia

Interventions

alvocidib; Lenalidomide

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kristie Blum

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2008
• First Posted: August 15, 2008
• Study Start: August 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: November 1, 2014
• Last Updated: April 2, 2015

Record last verified: 2015-02

Locations

US (1)