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LeukemiaPhase 1/2NCT00546377

Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer

A Phase 1/2 study testing filgrastim, pegfilgrastim and rituximab in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center 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

RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Leukemia, Lymphoma
What is being tested?
filgrastim, pegfilgrastim and rituximab
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Jul 2005to May 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following diseases confirmed by a Memorial Sloan-Kettering Cancer Center (MSKCC) pathologist:
  • Chronic lymphocytic leukemia meeting the following risk criteria as defined by the three-stage Rai system:
  • Intermediate-risk disease meeting the following criteria for active disease as defined by the NCI Working Group:
  • Weight loss
  • Fatigue
  • Fevers
  • Evidence of progressive marrow failure
  • Splenomegaly
  • Progressive lymphadenopathy
  • Progressive lymphocytosis with a rapid doubling time, defined as doubling time less than 6 months and absolute lymphocyte count > 30,000/μL
  • High-risk disease
  • Other low grade B-cell neoplasms, including any of the following:
  • Small lymphocytic lymphoma
  • Follicular lymphoma
  • Waldenstrom macroglobulinemia
  • Marginal zone lymphomas
  • Mantle cell lymphomas
  • Transformed lymphoma
  • Previously treated disease
  • Must have received prior cytotoxic therapy
  • Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found, may be enrolled regardless of serum bilirubin)
  • Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Normal cardiac ejection fraction ≥ 50% (increased ejection fraction [at least 5% over rest]) required for study eligibility
  • Borderline (40-50%) ejection fraction must undergo a stress echocardiogram or MUGA scan
  • Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment
  • Must have undergone consultation with the primary investigator or his/her designee prior to study entry
  • No significant active infections
  • No ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity
  • Hepatitis B antibody-positive patients are eligible

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • The following concurrent medications are allowed:
  • Intravenous immunoglobulin (IVIG)
  • Erythropoietin, darbepoetin, filgrastim, or sargramostim
  • Cyclosporine (only for patients with cellular immune cytopenias [i.e., pure red cell aplasia]), with required consultation of the principle investigator or designee
  • Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
  • No concurrent chemotherapy or radiotherapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I-II Study of Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Previously Treated Patients With Chronic Lymphocytic Leukemia and Other Low Grade B-Cell Neoplasms

RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving pentostatin together with combination chemotherapy and rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of mitoxantrone when given together with pentostatin, cyclophosphamide, and rituximab and to see how well it works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell cancer.

Read the detailed description

OUTLINE: This is a phase I, dose-escalation study of mitoxantrone hydrochloride followed by a phase II study.

  • Phase I: Patients receive pentostatin IV, cyclophosphamide IV, and mitoxantrone hydrochloride IV on day 1. Patients also receive rituximab IV on day 1 beginning in course 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Phase II: Patients receive pentostatin, cyclophosphamide, rituximab, and mitoxantrone hydrochloride (at the maximum tolerated dose determined in phase I) as in phase I.

All patients receive either pegfilgrastim subcutaneously (SC) on days 1-4 following each course or filgrastim or sargramostim SC beginning 2 days after each course until blood counts recover.

Patients undergo blood collection and bone marrow biopsy periodically for assessment of therapy response by biomarker and laboratory studies. Samples are analyzed for molecular genetics for IgH arrangement by PCR and for response by immunoelectrophoresis. Some samples are analyzed for response by flow cytometry or fluorescence in situ hybridization (FISH).

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 63 patients (18 patients for phase I and 45 patients for phase II) will be accrued for this study.

Conditions
Leukemia, Lymphoma
Keywords
B-cell chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, recurrent marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
Medical subject headings
Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular

What participants receive

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

Study groups in NCT00546377
Study groupRoleWhat they receive
MitoxantroneExperimentalNot described
Receives: Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Biological: sargramostim; Drug: cyclophosphamide; Drug: mitoxantrone hydrochloride; Drug: pentostatin; Genetic: fluorescence in situ hybridization; Genetic: gene rearrangement analysis; Genetic: polymerase chain reaction; Genetic: protein expression analysis; Other: flow cytometry; Procedure: biopsy

What is being measured

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

  1. Overall Response

    Complete response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment): it is recognized that some patients with lymphoid malignancies who achieve a CR may have mild persistent abnormalities on CT Scan. Such abnormalities if stable on subsequent scanning will not be viewed as persistent disease in patients who otherwise meet the criteria for CR. Response will be assessed on an ongoing basis, but at a minimum of prior to cycle four and following completion of all therapy. Patients who are removed from study early will have response status determined at time of removal from study. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.

    Measured: 3 years

  2. Maximum Tolerated Dose (MTD) of Mitoxantrone

    The MTD is defined as the highest dose studied for which the incidence of DLT is less than 33%. In the phase I portion of the trial, cohorts of 3-6 pts will receive pentostatin, cyclophosphamide and rituximab along with one of three potential dose levels of mitoxantrone. The following dose escalation scheme will be followed: If none of the initial three pts in a cohort experience a dose-limiting toxicity (grade 4 infection, or grade ≥ 3 non-hematologic toxicity that persists for 7 days or more) then a new cohort of three pts will be treated at the next higher dose level. If one of the three pts in a cohort experiences DLT, then up to three additional pts will be treated at the same dose level. If two or more pts in a cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. The previous dose level will be considered as the MTD.

    Measured: 2 years

Timeline

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

  1. First posted18 Oct 2007 (estimated)
  2. Study startJul 2005
  3. Primary completionMay 2014
  4. Study completionMay 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00546377
Sponsor's protocol ID
05-077
Other IDs
MSKCC-05077
Status last verified
Apr 2016
First submitted
17 Oct 2007
Last updated
12 May 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing filgrastim, pegfilgrastim and rituximab in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center 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?

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 12 May 2016. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response (time frame: 3 years). 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 NCT00546377.

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 12 May 2016; AzTrials last refreshed its copy on 7 Nov 2026.

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