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Chronic Lymphocytic LeukemiaPhase 1NCT01076556

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

A Phase 1 study testing Alvocidib Hydrochloride, Cyclophosphamide and Diagnostic Laboratory Biomarker Analysis in people with Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, 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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alvocidib Hydrochloride, Cyclophosphamide and Diagnostic Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Apr 2010to Jul 2010
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 chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic leukemia* (PLL) arising from CLL
  • Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point since initial diagnosis of CLL
  • Patients must have B-cells that co-express CD5 with CD19 or CD20
  • Patients who do not have dim sIg or CD23 expression on their leukemia cells should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle cell lymphoma
  • To be considered high risk, patients must meet the following criteria:
  • At least 1 of the following:
Show all 42Show fewer
  • 17p deletion
  • 11q deletion
  • Un-mutated IgV_H (≥ 98% homology)
  • Age > 70 years
  • B_2M > 4
  • AND at least 1 of the following:
  • Progressive or marked splenomegaly and/or lymphadenopathy
  • Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/mm^3)
  • Weight loss exceeding 10% of body weight over preceding 6 months
  • NCI grade 2 or 3 fatigue
  • Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection
  • Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of < 6 months
  • No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes)
  • No requirement for chronic corticosteroids
  • ECOG performance status 0-2
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease infiltration of the liver
  • AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No secondary or other malignancy that will limit survival to < 2 years
  • No uncontrolled concurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situations that would limit compliance with study requirements
  • No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication
  • No active hepatitis B infection
  • No known G6PD deficiency
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used in this study
  • No prior alvocidib
  • No prior purine analog therapy
  • No more than 1 prior treatment with a biologic or alkylating agent
  • No other concurrent investigational agents

Who cannot join

None listed.

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Alvocidib Hydrochloride, Cyclophosphamide, Diagnostic Laboratory Biomarker Analysis, Pharmacological Study, Rituximab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic

What participants receive

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

  • Alvocidib HydrochlorideDrug

    Also called 4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis-, Flavopiridol Hydrochloride, HL-275, HMR 1275

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Diagnostic Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • RituximabBiological

    Also called BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102

    Given IV

Study groups in NCT01076556
Study groupRoleWhat they receive
Treatment (rituximab, cyclophosphamide, alvocidib)ExperimentalPatients 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).
Receives: Drug: Alvocidib Hydrochloride; Drug: Cyclophosphamide; Other: Diagnostic Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Rituximab

What is being measured

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

  1. Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab

    Determined using the CTEP Active Version of the CTCAE.

    Measured: 21 days

  2. Treatment related adverse events assessed using the CTEP Active Version of the CTCAE

    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 posted26 Feb 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionJul 2010

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01076556
Sponsor's protocol ID
NCI-2011-01373
Other IDs
NCI-2011-01373, OSU 09089, CDR0000666448, OSU-09089, OSU 09089, 8267, P30CA016058, U01CA076576
Status last verified
Nov 2015
First submitted
25 Feb 2010
Last updated
11 Nov 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alvocidib Hydrochloride, Cyclophosphamide and Diagnostic Laboratory Biomarker Analysis in people with Chronic Lymphocytic Leukemia and Prolymphocytic 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 42 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 11 Nov 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 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?

Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab (time frame: 21 days). 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 NCT01076556.

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 11 Nov 2015.

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