AzTrials
AzTrials

AnemiaPhase 1NCT00735930

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

A Phase 1 study testing Alvocidib Hydrochloride, Lenalidomide and Pharmacological Study in people with Anemia and Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alvocidib Hydrochloride, Lenalidomide and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
Aug 2008to Nov 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 39Show fewer
  • 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
  • Recovery to =< grade 1 from all toxicities associated with prior therapy
  • Not pregnant or breast-feeding; woman of child bearing potential should have a negative pregnancy test (serum beta-human chorionic gonadotropin [HCG]) within 7-14 days of starting cycle 1 of treatment; woman of child bearing potential should have a negative pregnancy test (serum beta-HCG) within 10-14 days of starting cycle 2, the start of lenalidomide treatment (i.e. days 14-18 of cycle 1), and an additional test within 24 hours of starting cycle 2 treatment
  • Patient must agree to use adequate contraception for 4 weeks prior to the start of lenalidomide and up to 28 days following the last dose of lenalidomide to avoid risk of pregnancy
  • Women of child-bearing potential will be required to use two methods of birth control; one "highly effective method" and one "additional effective method" as defined below:
  • Highly effective methods
  • Intrauterine device
  • Hormonal (oral contraceptive, implants)
  • Tubal ligation
  • Partner's vasectomy
  • Abstinence
  • Alternative effective methods
  • Latex condoms
  • Diaphragm
  • Cervical cap
  • Men must agree to use latex condoms
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Patients must agree not to donate blood, semen, sperm/ova during the course of taking lenalidomide and for 28 days after stopping lenalidomide treatment
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • Patients who are glucose-6-phosphate dehydrogenase (G6PD) deficient are not eligible for this study
  • Only human immunodeficiency virus (HIV)-positive patients meeting all of the following criteria may be enrolled on this trial:
  • Cluster of differentiation (CD) 4 count > 500/mm^3
  • Not receiving highly active anti-retroviral therapy (HAART) or anti-HIV viral therapy
  • HIV viral load < 10,000 HIV messenger ribonucleic acid (mRNA) copies/mm^3
  • No history of acquired immune deficiency syndrome (AIDS)-defining illness

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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).

  1. 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.

Being tested
Alvocidib Hydrochloride, Lenalidomide, Pharmacological Study, Laboratory Biomarker Analysis
Medical subject headings
Anemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, Thrombocytopenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alvocidib HydrochlorideDrug

    Also called FLAVO, HL-275, HMR 1275

    Given IV

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, IMiD-1

    Given PO

  • Pharmacological StudyOther

    Also called pharmacological studies

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00735930
Study groupRoleWhat they receive
Treatment (alvocidib, lenalidomide)ExperimentalPatients 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.
Receives: Drug: Alvocidib Hydrochloride; Drug: Lenalidomide; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Up to day 70

  2. 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.

    Measured: Up to day 70

Secondary outcomes (8)

  1. Pharmacokinetic parameters of alvocidib and lenalidomide alone and in combination in plasma samples

    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.

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

  2. Plasma IL-6 and selected cytokine levels

    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.

    Measured: Up to 5 years

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

    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.

    Measured: Up to 5 years

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

    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.

    Measured: Up to 5 years

  5. Response assessed by National Cancer Institute-Sponsored Working Group guidelines

    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.

    Measured: Up to 5 years

  6. Progression-free survival (PFS)

    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.

    Measured: Time from start of treatment to time of progression, assessed up to 5 years

  7. Toxicity graded according to NCI CTCAE version 4.0

    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.

    Measured: Up to 5 years

  8. Presence of minimal residual disease

    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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionMar 2013
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00735930
Sponsor's protocol ID
NCI-2009-00269
Other IDs
NCI-2009-00269, OSU-08056, 2008C0033, CDR0000738866, OSU 08056, 8046, P30CA016058, U01CA076576
Status last verified
Feb 2015
First submitted
14 Aug 2008
Last updated
2 Apr 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alvocidib Hydrochloride, Lenalidomide and Pharmacological Study in people with Anemia and Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Up to day 70). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00735930.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in