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

NCT ID: NCT00669318

Last Updated: 2014-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2014-05-31

Brief 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. 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (Pentostatin, Alemtuzumab, Rituximab)

Course 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).

Group Type: EXPERIMENTAL

alemtuzumab

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

pentostatin

Intervention Type: DRUG

sargramostim

Intervention Type: DRUG

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

pentostatin

Intervention Type: DRUG

sargramostim

Intervention Type: DRUG

Other Intervention Names

GM-CSF

Eligibility Criteria

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clive S. Zent, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24723493 (View on PubMed)

Other Identifiers

LS0881

Identifier Type: OTHER

Identifier Source: secondary_id

08-000673

Identifier Type: OTHER

Identifier Source: secondary_id

LS0881

Identifier Type: -

Identifier Source: org_study_id