Pentostatin, Cyclophosphamide, and Rituximab Followed By Alemtuzumab in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00074282

Purpose

RATIONALE: Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab and alemtuzumab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well pentostatin, cyclophosphamide, rituximab, and alemtuzumab work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Biological: alemtuzumab Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Drug: cyclophosphamide Drug: pentostatin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Campath-1H for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cyclophosphamide Pentostatin Filgrastim Campath Rituximab Pegfilgrastim Alemtuzumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response rate as measured by percentage after pentostatin, cyclophosphamide, and rituximab (PCR) and Campath at 6 months and 12 months [ Designated as safety issue: No ]
Level of residual disease as measured by bone marrow and imaging studies at 6 months and 12 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as measured by CTCAE criteria every month [ Designated as safety issue: Yes ]
Overall survival and progression-free survival as measured by Kaplan-Meier method during study treatment [ Designated as safety issue: No ]
Conversion rate of complete remission after Campath therapy in partial remission patients as measured by the percent improvement rate after Campath [ Designated as safety issue: No ]

Estimated Enrollment:	110
Study Start Date:	December 2004
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the objective response rate (complete remission, partial remission [PR], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by alemtuzumab.
Determine the presence of minimal residual disease in patients treated with this regimen.

Secondary

Determine the toxicity of this regimen in these patients.
Determine the overall and progression-free survival of patients treated with this regimen.
Determine the number of patients who, after PCR, only achieve PR, stable disease, or progressive disease and subsequently convert to a higher response category after alemtuzumab.
Correlate V_H gene mutation status and CD38 expression of the CLL B-cell clones with clinical outcome in patients treated with this regimen.
Correlate the differential expression of genes in the leukemic cells with clinical outcome in patients treated with this regimen.
Correlate surface phenotype and genetic defects of the CLL B-cell clones with clinical outcome and gene expression patterns in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Pentostatin, cyclophosphamide, and rituximab (PCR)* therapy: Patients receive pentostatin IV over 10-30 minutes, cyclophosphamide IV over 30-60 minutes, and rituximab** IV on day 1. Patients also receive filgrastim (G-CSF) or pegfilgrastim subcutaneously (SC) beginning on day 3 and continuing until blood counts recover. Treatment repeats every 28 days for a total of 6 courses in the absence of unacceptable toxicity.

NOTE: *Patients demonstrating progression while receiving PCR must have completed 2 courses of PCR prior to proceeding to alemtuzumab therapy

NOTE: **Patients receive rituximab IV on days 1, 3, and 5 for course 1 only; for courses 2-6, patients receive rituximab on day 1 only

Alemtuzumab therapy: Twelve weeks after completion of PCR therapy, patients receive alemtuzumab SC on days 1, 3, and 5. In the absence of disease progression or unacceptable toxicity, treatment repeats weekly for 4 weeks for patients with complete remission or nodular partial remission (PR) after PCR OR for 18 weeks for patients with PR, stable disease, or progressive disease after PCR.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 26-110 patients will be accrued for this study within 1.5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:
- Peripheral blood absolute lymphocyte count greater than 5,000/mm^3
- Lymphocytosis must comprise small to moderate size lymphocytes with no greater than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
- Phenotypically characterized CLL defined by the following:
  - Predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3 or CD2)
  - B cell expresses either kappa or lambda light chains
  - Surface immunoglobulin with low cell surface density expression
Requires chemotherapy, as indicated by any of the following:
- Disease-related symptoms
  - Weight loss of 10% or more within the past 6 months
  - Extreme fatigue
  - Fevers greater than 100.5°F for 2 weeks without evidence of infection
  - Night sweats without evidence of infection
- Evidence of progressive marrow failure manifested by the development of or worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia (platelet count no greater than 100,000/mm^3)
- Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly
- Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy
- Progressive lymphocytosis with an increase of greater than 50% over a 2-month period OR an anticipated doubling time of less than 6 months
Demonstrated progression after at least 1 course of either an alkylating agent-based or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a meaningful response OR relapsed after prior therapy
- Patients who have relapsed after a pentostatin-based regimen are eligible provided the response was greater than 12 months prior to study entry
No bone marrow dysplasia related to prior therapy

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert's syndrome)

Renal

Creatinine no greater than 2.0 mg/dL OR
Creatinine clearance ≥ 30 mL/min

Cardiovascular

No New York Heart Association class III or IV heart failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy
No prior alemtuzumab
At least 8 weeks since prior rituximab

Chemotherapy

See Disease Characteristics
At least 6 weeks since prior chemotherapy
At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy
- PCR therapy at least 1 year prior to study entry allowed

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

No concurrent oral or IV antibiotics for active infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074282

Show 135 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Sanford J. Kempin, MD	St. Vincent's Comprehensive Cancer Center - Manhattan
Investigator:	Neil E. Kay, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Kay NE, Kim HT, Kempin S, et al.: Predictors of clinical outcome to pentostatin, cyclophosphamide and rituximab (PCR) followed by campath for relapsed/refractory CLL : a study of the Eastern Cooperative Oncology Group, E2903. [Abstract] Blood 112 (11): A-1057, 2008.

Kempin S, Kay NE, Sun Z, et al.: Early results of pentostatin, cytoxan, rituximab (PCR) followed by CAMPATH-H (CA) for the treatment of relapse/refractory chronic lymphocytic leukemia (CLL) in ECOG protocol E2903. [Abstract] Blood 110 (11): A-3109, 2007.

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000343796, ECOG-2903
Study First Received:	December 10, 2003
Last Updated:	August 21, 2009
ClinicalTrials.gov Identifier:	NCT00074282 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Study placed in the following topic categories:

Leukemia, Lymphoid
Pentostatin
Immunoproliferative Disorders
Immunologic Factors
Rituximab
Cyclophosphamide
Immunosuppressive Agents
Leukemia
Lymphatic Diseases

Chronic Lymphocytic Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Alemtuzumab
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Leukemia, B-Cell
Lymphoproliferative Disorders
Leukemia, B-cell, Chronic
Alkylating Agents

Additional relevant MeSH terms:

Leukemia, Lymphoid
Pentostatin
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Alemtuzumab
Therapeutic Uses
Alkylating Agents
Immunoproliferative Disorders

Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Leukemia, B-Cell
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 04, 2009