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LeukemiaPhase 2NCT00669318

Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

A Phase 2 study testing alemtuzumab, rituximab and pentostatin in people with Leukemia and Lymphoma, run by Mayo Clinic at 3 sites 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: Drugs used in chemotherapy, such as pentostatin, 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 alemtuzumab and rituximab, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Lymphoma
What is being tested?
alemtuzumab, rituximab and pentostatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
3 sitesUnited States
Study dates
Jul 2008to May 2014
Phase
Phase 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) meeting the following criteria:
  • Minimum threshold peripheral blood lymphocyte count of 5 x 10^9/L (CLL variant) OR adenopathy > 1 cm or palpable splenomegaly (SLL variant)
  • Immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) that are monoclonal (by light chain exclusion) AND have ≥ 3 of the following characteristics:
  • CD5+
  • CD23+
  • Dim surface light chain expression
  • Dim surface CD20 expression
  • FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression
  • Must have progressive disease as indicated by any of the following characteristics (based on standard criteria for treatment):
  • Symptomatic CLL characterized by any of the following:
  • Weight loss > 10% within the past 6 months
  • Extreme fatigue
  • Fevers > 38.5° C (not due to infection)
  • Drenching night sweats without evidence of infection
  • Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L
  • Massive and progressive splenomegaly (> 6 cm below left costal margin)
  • Massive (> 10 cm) or rapidly progressive lymphadenopathy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN
  • AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
  • Willing to provide mandatory blood samples for research studies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
  • No other active primary malignancy that requires treatment or limits survival to ≤ 2 years
  • No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
  • No New York Heart Association class III or IV heart disease
  • No myocardial infarction within the past month
  • No uncontrolled infection
  • No HIV infection or AIDS
  • No active hepatitis B infection (i.e., HBsAg or HBeAg positivity) or hepatitis C infection by serology
  • No other comorbid condition

PRIOR CONCURRENT THERAPY:

  • No more than 3 prior treatment regimens for CLL that included purine analogue drugs (e.g., fludarabine, pentostatin, or cladribine) OR previously untreated CLL in patients with high-risk disease due to 17p13 deletion on FISH analysis
  • More than 4 weeks since prior major surgery
  • More than 2 months since prior alemtuzumab
  • Prior corticosteroids allowed
  • No concurrent continuous systemic corticosteroids

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial

RATIONALE: Drugs used in chemotherapy, such as pentostatin, 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 alemtuzumab and 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 alemtuzumab and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving pentostatin together with alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Read the detailed description

OBJECTIVES:

Primary

  • To assess the rate of complete and overall response in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, alemtuzumab, and low-dose rituximab.
  • To monitor and assess toxicity of this treatment regimen.

Secondary

  • To determine the overall and progression-free survival, duration of response, and time to next treatment.
  • To assess the correlation between individual prognostic markers (17p-, 11q-, unmutated VH gene, VH3-21, ZAP-70+, CD38+, CD49d, and β2 microglobulin, miRNA profiles, angiogenesis status, and karyotypes of CpG stimulated cells) and clinical outcome.

OUTLINE: This is a multicenter study.

  • Course 1: Patients receive pentostatin IV on days 8 and 22; alemtuzumab subcutaneously (SC) on days 3-5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and sargramostim (GM-CSF) SC on days 10-14 and 24-28. Patients then proceed to course 2.
  • Courses 2 and 3: Patients receive pentostatin IV on days 1 and 15; alemtuzumab SC and rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; and GM-CSF SC on days 3-7 and 17-21. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood is collected on days 1, 3, 8, and 10 of course 1 for monoclonal antibody studies. Samples are analyzed for serum concentration of alemtuzumab and rituximab by ELISA and PCR; CH50 assay; complement activation and cytokine levels by ELISA; NK cell activation; and NK cell phenotype by immunofluorescent staining and flow cytometry.

After completion of study treatment, patients are followed up monthly for 6 months, every 3 months for 6 months, and then every 6-12 months for up to 5 years.

Conditions
Leukemia, Lymphoma
Being tested
alemtuzumab, rituximab, pentostatin, sargramostim
Keywords
refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

Study groups in NCT00669318
Study groupRoleWhat they receive
Treatment (Pentostatin, Alemtuzumab, Rituximab)ExperimentalCourse 1: Patients receive: * 2 mg/m^2 pentostatin IV on days 8 and 22; * 3 mg alemtuzumab subcutaneously (SC) on day 3; * 10 mg alemtuzumab SC on day 4; * 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; * 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; * 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: * 2 mg/m^2 pentostatin IV on days 1 and 15; * 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; * 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; * 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Receives: Biological: alemtuzumab; Biological: rituximab; Drug: pentostatin; Drug: sargramostim

What is being measured

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

  1. Complete Response Rate

    A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. In addition, a bone marrow biopsy with evidence of <30% lymphocytes and no nodules.

    Here we report the rate of complete response as the number of patients attaining a CR status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.

    Measured: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Secondary outcomes (4)

  1. Overall Response Rate (Complete and Partial Response)

    A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. A bone marrow biopsy with evidence of <30% lymphocytes and no nodules.

    Patients who fulfill all criteria for a CR but have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity will be classified as CR with incomplete marrow recovery (CRi).

    A Partial Response (PR) requires a 50% reduction in nodes and liver/spleen measurements and at least two of the following: absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, or a >50% reduction in lymphocytes.

    Here we report the rate of overall response as the number of patients attaining a CR, PR, or CRi status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.

    Measured: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

  2. Overall Survival

    Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: Follow-up status and retreatment information will be collected up to 5 years from registration

  3. Progression-free Survival

    The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

    Measured: Follow-up status and retreatment information will be collected up to 5 years from registration

  4. Time to Retreatment

    Time to subsequent therapy is defined to be the time from the registration to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier

    Measured: Follow-up status and retreatment information will be collected up to 5 years from registration

Timeline

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

  1. First posted30 Apr 2008 (estimated)
  2. Study startJul 2008
  3. Primary completionMay 2013
  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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00669318
Sponsor's protocol ID
LS0881
Other IDs
LS0881, 08-000673
Status last verified
Jun 2014
First submitted
29 Apr 2008
Last updated
1 Jul 2014
Data monitoring committee
Yes

Publications

  • Zent CS, Taylor RP, Lindorfer MA, Beum PV, LaPlant B, Wu W, Call TG, Bowen DA, Conte MJ, Frederick LA, Link BK, Blackwell SE, Veeramani S, Baig NA, Viswanatha DS, Weiner GJ, Witzig TE. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells. Am J Hematol. 2014 Jul;89(7):757-65. doi: 10.1002/ajh.23737. Epub 2014 Apr 26.

    PubMed 24723493

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alemtuzumab, rituximab and pentostatin in people with Leukemia and Lymphoma, run by Mayo Clinic at 3 sites 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 1 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 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 20 Jun 2014). 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?

Complete Response Rate (time frame: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)). 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 NCT00669318, 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 1 Jul 2014.

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