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Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Lenalidomide for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Lenalidomide for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia


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
lenalidomide.

- Determine the presence of minimal residual disease in patients treated with this
regimen.

Secondary

- Determine the toxicity of this regimen in these patients.

- Evaluate the toxicity of the combined therapy, PCR with lenalidomide, in patients with
previously treated B-CLL.

- 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
lenalidomide.

- 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.

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 lenalidomide, 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 lenalidomide treatment
and assess any association with clinical outcome and toxicities.

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) subcutaneously (SC) beginning on day 3 or
pegfilgrastim SC on day 1 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 lenalidomide 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.

Lenalidomide*** therapy: Eight weeks after completion of PCR therapy or when diagnosed with
progressive disease, patients receive lenalidomide orally (PO) on days 1-28. In the absence
of disease progression or unacceptable toxicity, treatment repeats every 28 days for
patients with partial remission (PR), stable disease, or progressive disease after PCR.
Patients who achieve complete remission proceed to clinical observation.

NOTE: ***The alemtuzumab therapy was replaced by lenalidomide therapy in May, 2011.

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.

Inclusion 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
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 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

- 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

- 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

- No prior lenalidomide

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- No concurrent oral or IV antibiotics for active infection

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response (CR, nPR, PR) rate in all patients treated with PCR

Safety Issue:

No

Principal Investigator

Sanford J. Kempin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Beth Israel Medical Center

Authority:

Unspecified

Study ID:

CDR0000343796

NCT ID:

NCT00074282

Start Date:

December 2004

Completion Date:

Related Keywords:

  • Leukemia
  • refractory chronic lymphocytic leukemia
  • B-cell chronic lymphocytic leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid

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Mayo Clinic ScottsdaleScottsdale, Arizona  85259
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CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
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CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Veterans Affairs Medical Center - East OrangeEast Orange, New Jersey  07018-1095
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Hinsdale Hematology Oncology AssociatesHinsdale, Illinois  60521
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
CCOP - MeritCare HospitalFargo, North Dakota  58122
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
St. Rita's Medical CenterLima, Ohio  45801
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Marshfield Clinic - Indianhead CenterRice Lake, Wisconsin  54868
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Ochsner Cancer Institute at Ochsner Clinic FoundationNew Orleans, Louisiana  70121
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Lewistown HospitalLewistown, Pennsylvania  17044
Mount Nittany Medical CenterState College, Pennsylvania  16803
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
Beth Israel Medical Center - Petrie DivisionNew York, New York  10003-3803
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Lakeland Regional Cancer Center at Lakeland Regional Medical CenterLakeland, Florida  33805
Hematology Oncology Associates - SkokieSkokie, Illinois  60076
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Hematology and Oncology AssociatesChicago, Illinois  60611
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Kellogg Cancer Care CenterHighland Park, Illinois  60035
Cancer Care and Hematology Specialists of Chicagoland - NilesNiles, Illinois  60714
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
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Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Ochsner Health Center - BluebonnetBaton Rouge, Louisiana  70809
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Marshfield Clinic - Chippewa CenterChippewa Falls, Wisconsin  54729
Marshfield Clinic Cancer Care at Regional Cancer CenterEau Claire, Wisconsin  54701
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Lakeland CenterMinocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's HospitalRhinelander, Wisconsin  54501
Marshfield Clinic at Saint Michael's HospitalStevens Point, Wisconsin  54481
Saint Michael's Hospital Cancer CenterStevens Point, Wisconsin  54481
Marshfield Clinic - Wausau CenterWausau, Wisconsin  54401
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Diagnostic and Treatment CenterWeston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids CenterWisconsin Rapids, Wisconsin  54494
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Trinity Cancer Center at Trinity Medical Center - 7th Street CampusMoline, Illinois  61265
Provena St. Mary's Regional Cancer Center - KankakeeKankakee, Illinois  60901
Ochsner Health Center - CovingtonCovington, Louisiana  70433
New Orleans Cancer Institute at Memorial Medical CenterNew Orleans, Louisiana  70115
Minnesota Oncology - MaplewoodMaplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
Lakeview HospitalStillwater, Minnesota  55082
Minnesota Oncology - WoodburyWoodbury, Minnesota  55125
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
Roger Maris Cancer Center at MeritCare HospitalFargo, North Dakota  58122
St. Nicholas HospitalSheboygan, Wisconsin  53081