Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT00816595 | Completed Phase 2 Results DMC

• 6 other identifiers: CDR0000630491P30CA015083RC078308-002080AVF4491sNCI-2009-01225
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, 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 and bevacizumab, 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. It is not yet known whether giving pentostatin and cyclophosphamide together with rituximab is more effective with or without bevacizumab in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. PURPOSE: This randomized phase II trial is studying the side effects of giving pentostatin and cyclophosphamide together with rituximab with or without bevacizumab and to see how well it works in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Leukemia; Lymphoma

Keywords

B-cell chronic lymphocytic leukemia; stage 0 chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete and Overall Response Rate

  A Complete Response (CR) requires all of the following for 2 months: * Absence of lymphadenopathy by physical examination (PE) * No hepato- or splenomegaly by PE * Neutrophils \>1500/ul, Platelets \>100,000/ul. Hemoglobin \>11.0 gm/dl, Peripheral blood lymphocytes \<4000/uL Nodular Partial Response (nPR) is defined as a patient qualified for a CR, but regenerative nodules are histologically present on bone marrow samples. A Clinical Complete Response (CCR) is defined as a patient qualified for a CR, but bone marrow samples are not available. A Partial Response (PR) requires 50% reduction in 2 of the following: peripheral blood lymphocytes, or the sum of the products of the maximal perpendicular diameters, or the size of liver and/or spleen; and a 50% increase in neutrophils, platelets, or hemoglobin. Overall response rate is calculated as the number of patients receiving CR, CCR, nPR, or PR as their objective status divided by the total number of evaluable patients.

  Evaluated after 6 cycles (up to 196 days)

Secondary Outcomes (2)

• Overall Survival

  Assessed up to 5 years from registration

• Progression-free Survival

  Assessed up to 5 years from registration

Study Arms (2)

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin

EXPERIMENTAL

Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m\^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m\^3 pentostatin IV over 30 minutes and 600 mg/m\^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: pentostatin

Arm B: Pentostatin, Cyclophosphamide, and Rituximab

EXPERIMENTAL

Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m\^2 on day 2 of course 1 and 375 mg/m\^2 on day 1 of courses 2-6. They receive 2 mg/m\^2 pentostatin IV over 30 minutes and 600 mg/m\^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: pentostatin

Interventions

bevacizumab BIOLOGICAL

Given IV

Also known as: Avastin

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin

pegfilgrastim BIOLOGICAL

Given subcutaneously

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin; Arm B: Pentostatin, Cyclophosphamide, and Rituximab

rituximab BIOLOGICAL

Given IV

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin; Arm B: Pentostatin, Cyclophosphamide, and Rituximab

cyclophosphamide DRUG

Given IV

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin; Arm B: Pentostatin, Cyclophosphamide, and Rituximab

pentostatin DRUG

Given IV

Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin; Arm B: Pentostatin, Cyclophosphamide, and Rituximab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Biopsy proven small lymphocytic lymphoma (SLL) * Chronic lymphocytic leukemia (CLL)\* as evidenced by the following criteria: * Peripheral blood lymphocyte count \> 5,000/mm³ consisting of small to moderate size lymphocytes * Immunophenotyping consistent with CLL, defined by the following: * The predominant population of lymphocytes share both B-cell antigens (CD19, CD20, or CD23) as well as CD-5 in the absence of other pan-T-cell markers (CD-3 or CD-2) * Dim surface immunoglobulin expression * Exclusively kappa and lambda light chains * Negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy samples NOTE: \*Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL * Has ≥ 1 of the following indications\*\* for chemotherapy: * Evidence of progressive marrow failure as manifested by the development of or worsening anemia (hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (platelet count ≤ 100,000/mm³) * Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly * Has ≥ 1 of the following disease-related symptoms: * Weight loss \> 10% within the past 6 months * Extreme fatigue attributed to CLL * Fevers \> 100.5\^oF for 2 weeks without evidence of infection * Night sweats without evidence of infection * Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of \> 50% over a 2-month period or an anticipated doubling time of \< 6 months NOTE: \*\*Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient indications for study treatment PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group performance status 0-3 * Life expectancy ≥ 12 months * Total bilirubin ≤ 3.0 times upper limit of normal (ULN) (unless due to Gilbert's disease) * Direct bilirubin \< 1.5 mg/dL (in patients with Gilbert's disease) * Serum glutamate oxaloacetate transaminase ≤ 3.0 times ULN (unless due to hepatic involvement by CLL) * Creatinine ≤ 1.5 times ULN * Urine protein:creatinine ratio \< 1.0 OR \< 1 g of protein by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 months after completion of study treatment * Willing to provide mandatory blood and tissue samples * None of the following cardiovascular conditions: * NYHA class III-IV heart disease * Myocardial infarction within the past 6 months * Unstable angina * Stroke, cerebrovascular accident, or transient ischemic attack within the past 6 months * Arterial thromboembolic events within the past 12 months * Clinically significant peripheral vascular disease * Uncontrolled hypertension, defined as systolic BP \> 150 mm Hg or diastolic BP \> 100 mm Hg * Hypertension allowed provided it is controlled with a stable anti-hypertensive regimen * History of hypertensive crises or hypertensive encephalopathy * Deep venous thromboses or pulmonary embolism within the past 12 months * No evidence of bleeding diathesis or coagulopathy * No uncontrolled or active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment * No active or recent history (within the past 30 days) of hemoptysis (≥ ½ teaspoon of bright red blood per episode) * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No active peptic ulcer disease * No serious non-healing wound, ulcer, or bone fracture * No significant traumatic injury within the past 28 days * No uncontrolled infection * No active HIV infection * No other active primary malignancy (except nonmelanoma skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting survival to ≤ 2 years * No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study participation PRIOR CONCURRENT THERAPY: * Prior corticosteroids allowed * More than 4 weeks since prior radiotherapy * More than 28 days since prior and no concurrent major surgical procedure or open biopsy * More than 7 days since prior minor surgical procedure, fine needle aspiration, or core biopsy (other than bone marrow biopsy) * No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin) * Doses of ≤ 2 mg daily allowed for prophylaxis of thrombosis * Prophylactic doses of low molecular weight heparin allowed * No other concurrent investigational agents for treatment of CLL or SLL * No other concurrent specific anticancer treatment except hormonal therapy

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 (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

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

Interventions

Bevacizumab; pegfilgrastim; Rituximab; Cyclophosphamide; Pentostatin

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Tait Shanafelt, M.D.
• Organization: Mayo Clinic

shanafelt.tait@mayo.edu

Study Officials

• Tait D. Shanafelt, MD

  Mayo Clinic

  STUDY CHAIR

• Jose F. Francisco, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 31, 2008
• First Posted: January 1, 2009
• Study Start: February 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: November 29, 2016
• Last Updated: June 15, 2017
• Results First Posted: May 9, 2014

Record last verified: 2017-05

Locations

US (2)