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B-cell Chronic Lymphocytic LeukemiaPhase 1NCT00058227

Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma

A Phase 1 study testing alvocidib, fludarabine phosphate and rituximab in people with B-cell Chronic Lymphocytic Leukemia and Contiguous Stage II Grade 1 Follicular Lymphoma, 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
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Trial summary

This phase I trial studies the side effects, best way to give, and the best dose of alvocidib when given together with fludarabine phosphate and rituximab in treating patients with previously untreated or relapsed lymphoproliferative disorders or mantle cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvocidib, fludarabine phosphate and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteUnited States
Study dates
Apr 2003to Feb 2009
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 mantle cell lymphoma OR indolent B-cell lymphoproliferative disorders of any of the following types:
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Follicular center cell non-Hodgkin's lymphoma (grade I or II)
  • Marginal zone lymphoma
  • Waldenstrom's macroglobulinemia
Show all 36Show fewer
  • Hairy cell leukemia
  • Previously untreated or relapsed/refractory disease
  • No evidence of histological transformation to an intermediate-grade or aggressive lymphoma
  • CD20 positive by immunoperoxidase or flow cytometry
  • Evaluable disease with presence of 1 of the following criteria:
  • Absolute lymphocyte count greater than 5,000/mm^3
  • At least 1 measurable node greater than 2 cm by computed tomography (CT) scan OR measurable disease in a lymphoid structure (spleen)
  • Bone marrow involvement (greater than 20% of marrow cellularity)
  • Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
  • See Disease Characteristics
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.0 g/dL
  • Bilirubin no greater than 2 times normal
  • Aspartate aminotransferase (AST) no greater than 2 times normal
  • Creatinine no greater than 2.0 mg/dL
  • Creatinine clearance at least 50 mL/min
  • No renal dysfunction that would impair tolerance or compliance with study therapy
  • No cardiac dysfunction that would impair tolerance or compliance with study therapy
  • No pulmonary dysfunction that would impair tolerance or compliance with study therapy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that would impair tolerability of compliance with therapy
  • No neurological or psychiatric dysfunction that would impair tolerability of or compliance with study therapy
  • At least 6 weeks since prior nitrosourea or mitomycin
  • No more than 6 prior courses of fludarabine
  • No concurrent corticosteroids as antiemetics
  • At least 4 weeks since prior therapy for disease
  • No more than 3 prior treatments for disease (not including steroids alone)

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 Study of Flavopiridol, Fludarabine and Rituximab in Indolent B-cell Lymphoproliferative Disorders and Mantle Cell Lymphoma

This phase I trial studies the side effects, best way to give, and the best dose of alvocidib when given together with fludarabine phosphate and rituximab in treating patients with previously untreated or relapsed lymphoproliferative disorders or mantle cell lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy such as alvocidib and fludarabine use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine a safe and tolerated dose of flavopiridol (alvocidib) in combination with standard dose rituximab and fludarabine (fludarabine phosphate) in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

II. To assess the toxicity of the combination regimen of flavopiridol, rituximab and fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

III. To determine the safety, toxicity and efficacy of administering flavopiridol as a 30-minute bolus followed by 4-hour infusion, in combination with rituximab and fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

SECONDARY OBJECTIVES:

  1. To determine pharmacokinetics of the combination regimen of flavopiridol, rituximab and fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

II. To determine pharmacodynamics of the combination regimen of flavopiridol, rituximab and fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

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

Patients receive fludarabine phosphate intravenously (IV) over 15-30 minutes on days 1-5 and rituximab IV over 3-4 hours on day 1. Alvocidib is administered IV over 60 minutes on day 1 in cohort 1; on days 1 and 2 in cohort 2; and on days 1, 2, and 3 in cohort 3. In cohorts 4 and 5, patients receive fludarabine phosphate and rituximab as above and alvocidib IV over 30 minutes and then IV over 4 hours on day 1 of courses 2-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Leukemia, Hairy Cell, Waldenstrom Macroglobulinemia

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

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00058227
Study groupRoleWhat they receive
Treatment (alvocidib, fludarabine phosphate, rituximab)ExperimentalPatients receive fludarabine phosphate IV over 15-30 minutes on days 1-5 and rituximab IV over 3-4 hours on day 1. Alvocidib is administered IV over 60 minutes on day 1 in cohort 1; on days 1 and 2 in cohort 2; and on days 1, 2, and 3 in cohort 3. In cohorts 4 and 5, patients receive fludarabine phosphate and rituximab as above and alvocidib IV over 30 minutes and then IV over 4 hours on day 1 of courses 2-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: alvocidib; Drug: fludarabine phosphate; Biological: rituximab; Other: pharmacological study

What is being measured

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

  1. Maximum tolerated dose (MTD) defined as that dose level beneath the dose at which 2 or more of 6 patients experience dose limiting toxicity (DLT)

    Measured: Day 28

  2. DLT defined as any grade 3-4 non-hematologic toxicity that does not resolve or decrease to grade 1-2 within 2 weeks, or any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy

    Measured: Day 28

Secondary outcomes (3)

  1. Toxicity as determined by National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 2.0 criteria

    Measured: Up to 6 years

  2. Pharmacokinetic data

    Measured: Up to 6 years

  3. Pharmacodynamic data

    Measured: Up to 6 years

Timeline

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

  1. First posted9 Apr 2003 (estimated)
  2. Study startApr 2003
  3. Primary completionFeb 2009

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
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00058227
Sponsor's protocol ID
NCI-2012-01434
Other IDs
OSU 0211, OSU-02H0281, CDR0000287196, NCI-5745, OSU-0211, U01CA076576
Status last verified
Jun 2013
First submitted
7 Apr 2003
Last updated
4 Jun 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alvocidib, fludarabine phosphate and rituximab in people with B-cell Chronic Lymphocytic Leukemia and Contiguous Stage II Grade 1 Follicular 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 36 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: finished, as of the sponsor's last update on 4 Jun 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 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?

Maximum tolerated dose (MTD) defined as that dose level beneath the dose at which 2 or more of 6 patients experience dose limiting toxicity (DLT) (time frame: Day 28). 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 NCT00058227.

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 4 Jun 2013.

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