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B-cell Chronic Lymphocytic LeukemiaPhase 1NCT00377104

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

A Phase 1 study testing alvocidib, pharmacological study and laboratory biomarker analysis in people with B-cell Chronic Lymphocytic Leukemia and Contiguous Stage II Small Lymphocytic Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvocidib, pharmacological study and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Sep 2006to Nov 2012
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

  • Diagnosis of 1 of the following:
  • B-cell chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • Must have received 1-3 prior therapies for CLL
  • Completed therapy 2-12 months ago
  • Prior therapy must have led to a partial response or greater
Show all 28Show fewer
  • No evidence of progressive disease
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,000/mm³
  • WBC ≤ 5,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Cytopenia allowed
  • Creatinine < 2.0 mg/dL
  • Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
  • AST ≤ 2 times normal (unless due to hemolysis)
  • No secondary malignancy or other disease that would limit survival to < 2 years
  • No history of inflammatory bowel disease unless inactive for > 2 years
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • See Disease Characteristics
  • No other concurrent chemotherapy
  • No concurrent radiotherapy
  • No concurrent dexamethasone or other corticosteroid-based antiemetics
  • No concurrent chronic corticosteroid therapy
  • No other concurrent hormonal therapy except for the following:
  • Steroids for new adrenal failure
  • Hormones for nondisease-related conditions (e.g., insulin for diabetes)

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

SECONDARY OBJECTIVES:

  1. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.

II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.

OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.

Treatment repeats every 5 weeks for up to 2 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. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.

After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.

Being tested
alvocidib, pharmacological study, laboratory biomarker analysis
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • alvocidibDrug

    Also called FLAVO, flavopiridol, HMR 1275, L-868275

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00377104
Study groupRoleWhat they receive
Treatment (chemotherapy)ExperimentalPatients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: alvocidib; 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. Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy

    Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.

    Measured: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment

  2. Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma

    The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity. If no patients experience dose-limiting toxicity, dose escalation will occur. If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose. If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients. If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.

    Measured: Course 1

Secondary outcomes (2)

  1. Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule

    Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine. We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.

    Measured: Baseline and day 1

  2. Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL

    Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.

    Measured: Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment

Timeline

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

  1. First posted15 Sep 2006 (estimated)
  2. Study startSep 2006
  3. Primary completionNov 2012

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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00377104
Sponsor's protocol ID
NCI-2009-00161
Other IDs
OSU 05116, OSU-IRB-2006C0031, CDR0000501975, OSU-05116, U01CA076576
Status last verified
Jul 2013
First submitted
13 Sep 2006
Last updated
2 Jul 2013
Results posted
No

Publications

  • Awan FT, Jones JA, Maddocks K, Poi M, Grever MR, Johnson A, Byrd JC, Andritsos LA. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy. Ann Hematol. 2016 Jun;95(7):1137-43. doi: 10.1007/s00277-016-2683-1. Epub 2016 Apr 27.

    PubMed 27118540

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alvocidib, pharmacological study and laboratory biomarker analysis in people with B-cell Chronic Lymphocytic Leukemia and Contiguous Stage II Small Lymphocytic Lymphoma, 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 28 inclusion and 0 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: stopped early, as of the sponsor's last update on 2 Jul 2013. 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 was stopped early. Results are not available in the source record.

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?

Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy (time frame: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment). 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 NCT00377104, which also lists 1 linked publication.

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 Jul 2013.

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