Clinical trial NCT00074282: Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-12-11
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and CAMPATH-1H work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab 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 CAMPATH-1H work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.

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 CAMPATH-1H .
* Determine the presence of minimal residual disease in patients treated with this regimen who achieve a CR or nPR

Secondary

* Determine the toxicity of this regimen in these patients.
* Determine the overall and progression-free survival of patients treated with this regimen.
* Evaluate the number of patients who after PCR (or during PCR for PD), only achieve a PR, SD, or PD and who subsequently convert to a higher response category after CAMPATH-1H .

Exploratory

* Assess the angiogenic profile (i.e., secretion levels of pro- versus anti-angiogenic molecules) of CLL B cell clones as well as bone marrow angiogenesis (i.e., vascular density by immunohistochemistry) at baseline, after PCR, after CAMPATH-1H, every six months (serum only), and at time of response assessment (marrow).
* Determine the V_H gene mutation status and CD38 expression of the B-CLL clones at study entry and at the end of the therapy and assess the association between the VH gene mutation status and CD38 expression and clinical outcome.
* Determine surface phenotype (by flow cytometry) and genetic defects (by CLL FISH panel) information on CLL-B cell clones and associate with clinical outcome.
* Monitor the T-cell status by repertoire and flow cytometry analysis to determine the nature and extent of T-cell deficiency induced by the PCR and CAMPATH-1H treatment and assess any association with clinical outcome and toxicities.

Eligibility criteria: Inclusion criteria:

* 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
* 18 and over
* ECOG Performance Status 0-2
* Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome)
* Creatinine no greater than 2.0 mg/dL
* Creatinine clearance ≥ 30 mL/min
* Negative pregnancy test
* Fertile patients must use 2 methods of effective contraception (including 1 barrier method) for at least 28 days before starting lenalidomide, while participating in the study, and for at least 28 days after discontinuation/stopping lenalidomide
* At least 8 weeks since prior rituximab
* 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

Exclusion criteria:

* Bone marrow dysplasia related to prior therapy
* New York Heart Association class III or IV heart failure
* Prior lenalidomide
* Other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
* Pregnant or nursing
* Concurrent oral or IV antibiotics for active infection

Primary outcomes:
measure: Response Rate
timeFrame: 8 weeks after Cycle 6
measure: Molecular Complete Remission (MCR) Rate
timeFrame: 3 months post alemtuzumab
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 5 years from registration
measure: Progression-free Survival (PFS)
timeFrame: Up to 5 years from registration
measure: Number of Patients Who After PCR (or During PCR for PD), Only Achieve a PR, SD, or PD and Who Subsequently Convert to a Higher Response Category After Campath-1H
timeFrame: From re-registration up to 5 years (followed for response until progression)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: St. Mary - Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center at Lakeland Regional Medical Center
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Highland Park
country: United States
facility: Kellogg Cancer Care Center
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Kankakee
country: United States
facility: Provena St. Mary's Regional Cancer Center - Kankakee
state: Illinois
city: Libertyville
country: United States
facility: North Shore Oncology and Hematology Associates, Limited - Libertyville
state: Illinois
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland - Niles
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates - Skokie
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas, PA - Liberal
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baton Rouge
country: United States
facility: Ochsner Health Center - Bluebonnet
state: Louisiana
city: Covington
country: United States
facility: Ochsner Health Center - Covington
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans Cancer Institute at Memorial Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Bemidji
country: United States
facility: MeritCare Bemidji
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology - Woodbury
state: Minnesota
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: New York
country: United States
facility: Beth Israel Medical Center - Petrie Division
state: New York
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: Roger Maris Cancer Center at MeritCare Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Hazleton Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Chippewa Falls
country: United States
facility: Marshfield Clinic - Chippewa Center
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Medical Center Cancer Care Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Marshfield
country: United States
facility: Saint Joseph's Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Sheboygan
country: United States
facility: St. Nicholas Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic at Saint Michael's Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Saint Michael's Hospital Cancer Center
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic - Wausau Center
state: Wisconsin
city: Weston
country: United States
facility: Diagnostic and Treatment Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Beth Israel Medical Center
name: Sanford J. Kempin, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.