- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00816595
Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab With or Without Concurrent Avastin® for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL)
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- To assess the rate of complete and overall response in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, cyclophosphamide, and rituximab with or without bevacizumab.
- To assess the proportion of patients who achieve a negative minimal residual disease state after treatment with these regimens.
- To monitor and assess the adverse events of these regimens.
Secondary
- To determine if molecular prognostic parameters (ZAP-70, CD38, cytogenetic abnormalities identified by FISH, and IgVH mutation status) relate to response in these patients.
- To determine the progression-free survival of patients treated with these regimens.
- To complete additional correlative studies to gain insight into disease biology and how it influences drug sensitivity.
OUTLINE: Patients are stratified according to Rai risk group (high [Rai stage III or IV] vs low [Rai stage 0] or intermediate [Rai stage I or II]) and FISH prognosis group (favorable [normal, +12, 13q-, or other] vs unfavorable [17p- or 11q-]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 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.
NOTE: *Course 6 is 56 days in duration
- Arm II: Patients receive rituximab IV over 2-4 hours on days 1 and 2 of course 1 and on day 1 of courses 2-6 and pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1. Patients also receive pegfilgrastim SC on day 2. Treatment repeats every 21 days* for 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Course 6 is 56 days in duration
Patients undergo blood sample collection and bone marrow biopsy/aspiration periodically for translational research studies. Samples are analyzed by flow cytometry for assessment of minimal residual disease. Molecular prognostic markers (including CD38, ZAP-70, IgVH gene mutation status, and cytogenetic abnormalities by FISH), Tcl-1 and CD49d protein expression, and immunoglobulin heavy chain D and J family gene usage are also analyzed. Plasma samples are stored for future studies evaluating levels of VEGF, bFGF, and thrombospondin by ELISA.
After completion of study therapy, patients are followed periodically for up to 5 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin
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.
|
Given IV
Other Names:
Given IV
Given IV
Given subcutaneously
Given IV
|
Experimental: Arm B: Pentostatin, Cyclophosphamide, and Rituximab
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.
|
Given IV
Given IV
Given subcutaneously
Given IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete and Overall Response Rate
Time Frame: Evaluated after 6 cycles (up to 196 days)
|
A Complete Response (CR) requires all of the following for 2 months:
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Assessed up to 5 years from registration
|
The Kaplan-Meier method will be used to estimate overall survival distributions Overall survival is measured as the time from registration to the time of death due to any cause.
|
Assessed up to 5 years from registration
|
Progression-free Survival
Time Frame: Assessed up to 5 years from registration
|
The Kaplan-Meier method will be used to estimate progression-free survival distribution.
Progression-free survival is defined as the time from registration to the time of progression or death, whichever occurs first.
|
Assessed up to 5 years from registration
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Tait D. Shanafelt, MD, Mayo Clinic
- Principal Investigator: Jose F. Francisco, M.D., Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- B-cell chronic lymphocytic leukemia
- stage 0 chronic lymphocytic leukemia
- stage I chronic lymphocytic leukemia
- noncontiguous stage II small lymphocytic lymphoma
- stage I small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- contiguous stage II small lymphocytic lymphoma
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Lymphoma
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Adenosine Deaminase Inhibitors
- Cyclophosphamide
- Bevacizumab
- Rituximab
- Pentostatin
Other Study ID Numbers
- CDR0000630491
- P30CA015083 (U.S. NIH Grant/Contract)
- RC0783 (Registry Identifier: Mayo Clinic Cancer Center)
- 08-002080 (Other Identifier: Mayo Clinic IRB)
- AVF4491s (Other Identifier: Genentech protocol)
- NCI-2009-01225 (Registry Identifier: NCI CTRP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lymphoma
-
Marcela V. Maus, M.D.,Ph.D.RecruitingFollicular Lymphoma | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Diffuse Large B Cell Lymphoma | Refractory Non-Hodgkin Lymphoma | Primary Mediastinal Large B-cell Lymphoma (PMBCL) | Non-hodgkin Lymphoma | High-grade B-cell Lymphoma | Grade 3b Follicular Lymphoma | Relapsed Non-Hodgkin LymphomaUnited States
-
Novartis PharmaceuticalsBristol-Myers SquibbRecruitingNon-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone LymphomaUnited States, Germany, Italy, Korea, Republic of, Spain, Singapore, China, Japan, Australia
-
IGM Biosciences, Inc.ADC Therapeutics S.A.Active, not recruitingFollicular Lymphoma | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Non-Hodgkin Lymphoma | DLBCLUnited States, Korea, Republic of, Spain, France, Australia, Czechia, Italy
-
Zhejiang UniversityShanghai First Song Therapeutics Co., LtdNot yet recruitingHodgkin Lymphoma | Anaplastic Large Cell Lymphoma | Angioimmunoblastic T-cell Lymphoma | Diffuse Large B Cell Lymphoma | Gray Zone Lymphoma | NK/T Cell Lymphoma | Peripheral T Cell Lymphoma, Unspecified | Mediastinal B-Cell Diffuse Large Cell LymphomaChina
-
Massachusetts General HospitalTG TherapeuticsTerminatedLymphoma | Follicular Lymphoma | Marginal Zone Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma Grade IIIa | Marginal Zone B Cell Lymphoma | Follicular Lymphoma Grade 2United States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedFollicular Lymphoma | Mantle Cell Lymphoma | Non-Hodgkin Lymphoma | B-Cell Non-Hodgkin Lymphoma | Adult Diffuse Large B-Cell Lymphoma | T-Cell Non-Hodgkin LymphomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedMantle Cell Lymphoma | Marginal Zone Lymphoma | Non-Hodgkin Lymphoma | Small Lymphocytic Lymphoma | Lymphoproliferative Disorder | Primary Cutaneous B-Cell Non-Hodgkin Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Primary Cutaneous T-Cell Non-Hodgkin Lymphoma | Grade 3 Follicular... and other conditionsUnited States, Canada, Australia, Puerto Rico
-
SymBio PharmaceuticalsCompletedFollicular Lymphoma | Non-Hodgkin's Lymphoma | Lymphoma, Large Cell | Diffuse, Mantle Cell Lymphoma, Lymphoma | Large B-Cell, DiffuseJapan, Korea, Republic of
-
Massachusetts General HospitalNational Comprehensive Cancer NetworkCompletedFollicular Lymphoma | Mantle Cell Lymphoma | Non-Hodgkin Lymphoma | Peripheral T-cell Lymphoma | Diffuse Large B-cell LymphomaUnited States
-
Novartis PharmaceuticalsCompletedDiffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular LymphomaUnited States, Belgium, Germany, France, Italy, Korea, Republic of, Spain, Turkey
Clinical Trials on bevacizumab
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Serous Cystadenocarcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Recurrent... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologyCompletedGlioblastoma | Gliosarcoma | Recurrent Glioblastoma | Oligodendroglioma | Giant Cell Glioblastoma | Recurrent Brain NeoplasmUnited States, Canada
-
M.D. Anderson Cancer CenterRecruitingStage IB Hepatocellular Carcinoma AJCC v8 | Stage II Hepatocellular Carcinoma AJCC v8 | Resectable Hepatocellular Carcinoma | Stage I Hepatocellular Carcinoma AJCC v8 | Stage IA Hepatocellular Carcinoma AJCC v8United States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Fallopian Tube Clear Cell Adenocarcinoma | Fallopian Tube Endometrioid Adenocarcinoma | Fallopian Tube Serous Adenocarcinoma and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Stage IVA Cervical Cancer AJCC v6 and v7 | Recurrent Cervical Carcinoma | Stage IV Cervical Cancer AJCC v6 and v7 | Stage IVB Cervical Cancer AJCC v6 and v7United States
-
Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingStage IV Cutaneous Melanoma AJCC v6 and v7 | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; Celldex TherapeuticsRecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Endometrial Serous Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Recurrent Fallopian... and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingMalignant Solid Neoplasm | Ovarian Endometrioid Adenocarcinoma | Ovarian Undifferentiated Carcinoma | Cervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Malignant Peritoneal Neoplasm | Endometrial Clear Cell Adenocarcinoma | Endometrial Endometrioid Adenocarcinoma | Endometrial Mixed Cell... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Lung Non-Small Cell Carcinoma | Stage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage IIIC Lung Cancer AJCC v8 | Locally Advanced Lung Non-Small... and other conditionsUnited States