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

NCT00669318 | Completed Phase 2 Results DMC

• 2 other identifiers: LS088108-000673
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

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.

Conditions

Leukemia; Lymphoma

Keywords

refractory chronic lymphocytic leukemia; recurrent small lymphocytic lymphoma; B-cell chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Overall Response Rate (Complete and Partial Response)

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

• Overall Survival

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

• Progression-free Survival

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

• Time to Retreatment

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

Study Arms (1)

Treatment (Pentostatin, Alemtuzumab, Rituximab)

EXPERIMENTAL

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).

Biological: alemtuzumab; Biological: rituximab; Drug: pentostatin; Drug: sargramostim

Interventions

alemtuzumab BIOLOGICAL

Treatment (Pentostatin, Alemtuzumab, Rituximab)

rituximab BIOLOGICAL

Treatment (Pentostatin, Alemtuzumab, Rituximab)

pentostatin DRUG

Treatment (Pentostatin, Alemtuzumab, Rituximab)

sargramostim DRUG

Also known as: GM-CSF

Treatment (Pentostatin, Alemtuzumab, Rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 24723493 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; Rituximab; Pentostatin; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Timothy G. Call MD
• Organization: Mayo Clinic Cancer Center

call.timothy@mayo.edu

Study Officials

• Clive S. Zent, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: April 30, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: July 1, 2014
• Results First Posted: June 20, 2014

Record last verified: 2014-06

Locations

US (3)