Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study Details
Study Description
Brief Summary
RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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, 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 cyclophosphamide and rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects and how well giving pentostatin together with cyclophosphamide and rituximab works in treating patients with previously untreated chronic lymphocytic leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
-
To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab.
-
To characterize the toxicity of this regimen in these patients.
OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course
- Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at least every 3 months for 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: cyclophosphamide, pentostatin & rituximab Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Biological: rituximab
Drug: cyclophosphamide
Drug: pentostatin
|
Outcome Measures
Primary Outcome Measures
- Overall Objective Response [2 years]
The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells
-
Previously untreated disease
-
Meets 1 of the following risk criteria as defined by the three-stage Rai system
-
Intermediate-risk disease
-
Must meet the criteria for active disease as defined by the NCI Working
Group guidelines including the following:
-
Weight loss
-
Fatigue
-
Fevers
-
Evidence of progressive marrow failure
-
Splenomegaly
-
Progressive lymphadenopathy
-
Progressive lymphocytosis with a rapid doubling time
-
High-risk disease
-
Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis
-
Patients with small lymphocytic lymphoma (CLL type) are eligible
PATIENT CHARACTERISTICS:
Inclusion criteria:
-
Karnofsky performance status 60-100%
-
Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin)
-
Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
-
Not pregnant or nursing
-
Fertile patients must use effective contraception
-
Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage
Exclusion criteria:
-
Significant active infections
-
Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity
-
Patients who are hepatitis B antibody positive are eligible for this protocol
PRIOR CONCURRENT THERAPY:
-
Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
-
No prior cytotoxic therapy or rituximab for this cancer
-
No concurrent radiotherapy or other chemotherapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute (NCI)
- Astex Pharmaceuticals, Inc.
Investigators
- Principal Investigator: Nicole Lamanna, MD, Memorial Sloan Kettering Cancer Center
- Principal Investigator: Renier Brentjens, MD, PhD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 05-051
- P30CA008748
- MSKCC-05051
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | All patients who received cyclophosphamide, pentostatin and rituximab |
| Period Title: Overall Study | |
| STARTED | 49 |
| COMPLETED | 46 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | All patients who received cyclophosphamide, pentostatin and rituximab |
| Overall Participants | 49 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
31
63.3%
|
| >=65 years |
18
36.7%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
24.5%
|
| Male |
37
75.5%
|
Outcome Measures
| Title | Overall Objective Response |
|---|---|
| Description | The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Patients |
|---|---|
| Arm/Group Description | All patients who received cyclophosphamide, pentostatin and rituximab |
| Measure Participants | 46 |
| Complete Response (CR) |
10
20.4%
|
| Nodular Response |
5
10.2%
|
| Partial Response (PR) |
26
53.1%
|
| Stable Disease (SD) |
4
8.2%
|
| Progression of Disease (POD) |
1
2%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | All Patients | |
| Arm/Group Description | All patients who received cyclophosphamide, pentostatin and rituximab | |
All Cause Mortality |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 18/49 (36.7%) | |
| Cardiac disorders | ||
| Hypertension | 2/49 (4.1%) | |
| General disorders | ||
| Dizziness | 1/49 (2%) | |
| Dyspnea | 3/49 (6.1%) | |
| Facial pain | 1/49 (2%) | |
| Febrile neutropenia | 5/49 (10.2%) | |
| Localized edema | 1/49 (2%) | |
| Pharyngeal mucositis | 1/49 (2%) | |
| Pneumonia | 9/49 (18.4%) | |
| Immune system disorders | ||
| Immune system disorder | 1/49 (2%) | |
| Infections and infestations | ||
| Tooth infection | 1/49 (2%) | |
| Musculoskeletal and connective tissue disorders | ||
| Joint pain | 1/49 (2%) | |
| Muscle weakness lower limb | 1/49 (2%) | |
| Muscle weakness upper limb | 1/49 (2%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash desquamating | 1/49 (2%) | |
Other (Not Including Serious) Adverse Events |
||
| All Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 49/49 (100%) | |
| Blood and lymphatic system disorders | ||
| ALT, SGPT | 9/49 (18.4%) | |
| AST, SGOT | 4/49 (8.2%) | |
| Hemoglobin | 42/49 (85.7%) | |
| Leukocytes (total WBC) | 39/49 (79.6%) | |
| Lymphopenia | 31/49 (63.3%) | |
| Neutrophils/granulocytes (ANC/AGC) | 46/49 (93.9%) | |
| Platelets | 21/49 (42.9%) | |
| Gastrointestinal disorders | ||
| Distension/bloating, abdominal | 3/49 (6.1%) | |
| Nausea | 4/49 (8.2%) | |
| General disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 6/49 (12.2%) | |
| Pain | 3/49 (6.1%) | |
| Tumor lysis syndrome | 4/49 (8.2%) | |
| Metabolism and nutrition disorders | ||
| Albumin, low (hypoalbuminemia) | 4/49 (8.2%) | |
| Bilirubin (hyperbilirubinemia) | 9/49 (18.4%) | |
| Creatinine | 3/49 (6.1%) | |
| Glucose, high (hyperglycemia) | 32/49 (65.3%) | |
| Phosphate, low (hypophosphatemia) | 13/49 (26.5%) | |
| Potassium, high (hyperkalemia) | 7/49 (14.3%) | |
| Sodium, low (hyponatremia) | 3/49 (6.1%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Renier Brentjens |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 1212-639-7053 |
| brentjer@mskcc.org |
- 05-051
- P30CA008748
- MSKCC-05051