Early or Delayed Fludarabine and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Terminated
CT.gov ID
NCT00513747
Collaborator
National Cancer Institute (NCI) (NIH)
84
Enrollment
387
Locations
2
Arms
101
Duration (Months)
0.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, 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 fludarabine together with rituximab may kill more cancer cells. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving fludarabine together with rituximab early is more effective than giving fludarabine and rituximab after observation in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine and rituximab to compare how well they work when given early or after observation in treating patients with previously untreated chronic lymphocytic leukemia.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: rituximab
  • Drug: fludarabine phosphate
Phase 3

Detailed Description

OBJECTIVES:

Primary

  • To determine if early treatment with chemoimmunotherapy comprising fludarabine phosphate and rituximab extends the time to second treatment in patients with genetically high-risk (unmutated IgV_H), asymptomatic, previously untreated chronic lymphocytic leukemia (CLL).

  • To determine the time to disease progression that would warrant second treatment.

  • To determine overall survival.

Secondary

  • To measure the proportion of patients with asymptomatic, previously untreated CLL who have mutated and unmutated IgV_H genes.

  • To determine the differences in acute and chronic toxicity of administering chemoimmunotherapy early to patients with genetically high-risk CLL compared to waiting until symptoms develop.

  • To determine the effect of select pretreatment clinical and biological characteristics (such as interphase cytogenetic abnormalities, ZAP-70 expression, and p53 dysfunction [primary and secondary]) on response, time to second treatment, and overall survival of patients with genetically high-risk CLL randomized to early treatment.

  • To determine the effect of select pretreatment clinical and biological characteristics (such as interphase cytogenetic abnormalities, ZAP-70 expression, and p53 dysfunction) on response, time to first and second treatments, and overall survival of patients with genetically high-risk CLL randomized to standard treatment (observation until symptoms occur).

  • To describe the natural history of patients with genetically low-risk (mutated IgV_H genes), asymptomatic, previously untreated CLL, in terms of time to initial treatment, response, progression, and survival.

  • To determine the effect of select pretreatment characteristics on time to first treatment, response, progression, and survival of patients with genetically low-risk CLL.

  • To correlate patterns of resistance that emerge in patients with unmutated IgV_H genes who have relapsing or refractory CLL following receipt of chemoimmunotherapy with clonal evolution, including acquisition of high-risk karyotype abnormalities, p53 mutations, p53 dysfunction (primary and secondary), altered mRNA and protein expression related to treatment resistance, DNA mutations, microRNA gene expression, and methylation changes.

  • To determine whether highly sensitive flow cytometry negativity at completion of therapy in patients randomized to early treatment is an effective surrogate marker for prolonged time to second treatment, overall survival, and other clinical benefits.

  • To collect demographic data on familial CLL in newly diagnosed patients participating on this study.

OUTLINE: This is a multicenter study.

  • Genetically high-risk disease: Patients are stratified according to age (< 50 years vs 50 to 70 years vs > 70 years) and presence of the high-risk genetic feature [del(11)(q22.3) or del(17)(p13.1)] by FISH (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive rituximab IV over 4 hours on days 1, 3, and 5 of week 1 and then on day 1 of weeks 5, 9, 13, 17, and 21. Patients also receive fludarabine phosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.

  • Arm II: Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.

  • Genetically low-risk disease: Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.

Patients undergo blood sample collection periodically for correlative studies.

After finishing treatment, patients are followed periodically.

Study Design

Study Type:
Interventional
Actual Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Intergroup CLL Study of Asymptomatic Patients With Untreated Chronic Lymphocytic Leukemia Randomized to Early Intervention Versus Observation With Later Treatment in the High Risk Genetic Subset With IGVH Unmutated Disease
Study Start Date :
Jan 1, 2008
Actual Primary Completion Date :
Jun 1, 2016
Actual Study Completion Date :
Jun 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I

Patients receive rituximab IV over 4 hours on days 1, 3, and 5 of week 1 and then on day 1 of weeks 5, 9, 13, 17, and 21. Patients also receive fludarabine phosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.

Biological: rituximab
Given IV over 4 hours

Drug: fludarabine phosphate
Given IV over 30 minutes

Active Comparator: Arm II

Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.

Biological: rituximab
Given IV over 4 hours

Drug: fludarabine phosphate
Given IV over 30 minutes

Outcome Measures

Primary Outcome Measures

  1. Time to Second Treatment in High Risk Patients [Up to 72 months]

    Kaplan-Meier analysis was conducted to estimate the distribution of time from randomization to second treatment or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.

  2. Disease-Free Survival in High Risk Patients [Up to 72 months]

    Kaplan-Meier analysis was conducted to estimate disease free survival defined as:> Arm A: Time from randomization until Second Treatment (first relapse) or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.> Arm B: Time from randomization until First Treatment (first relapse) or death whichever comes first. Events were defined as the start of first treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.

  3. Overall Survival (OS) for High Risk Patients [Up to 72 months]

    Kaplan-Meier analysis was conducted to estimate the distribution of time from randomization to death from any cause. Estimates were not stratified. Patients who did not experience this primary outcome had their survival times censored at their last follow-up.

Secondary Outcome Measures

  1. Number of Patients With Mutated and Unmutated IgVH Genes [Once at baseline]

    Number of patients with mutated and unmutated IgVH genes are reported below.

  2. Overall Survival in Low Risk Patients [Up to 72 months]

    Overall survival in low risk patients (registration to first treatment or death)> • Events were defined as death from any cause. Low risk Patients who were alive were censored at their last known follow-up.

  3. Time to First Treatment Survival in Low Risk Patients [Up to 72 months]

    Time to First Treatment Survival in low risk patients (registration to first treatment or death)> • Events were defined as the start of first treatment or death from any cause. Patients who didn't receive their first treatment were censored at their last known follow-up.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Eligibility Criteria for Pre-Registration:
  1. Patients must be within 6 months of the initial flow cytometric confirmation of B-cell chronic lymphocytic leukemia (CLL). This interval begins with the initial flow cytometric confirmation of disease.

  2. Clinical and immunophenotypic evidence of CLL including:

2.1 An absolute lymphocytosis of > 5,000/μL

  • Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes.

  • Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers.

  • Additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density.

  • Patients with bright surface immunoglobulin levels must have CD23 coexpression and absence of t(11;14) on interphase cytogenetics or have negative tumor protein staining for cyclin D1.

2.2 Staging - Patients must be in the low category (i.e., only stages 0 or I) of the modified three-stage Rai staging system as described in the protocol.

  1. Patients should not have evidence of active disease as demonstrated by any of the following criteria:
  • Splenomegaly and/or massive/progressive lymphadenopathy that would require therapy

  • Presence of weight loss > 10% over the preceding 6 month period

  • Grade 2 or 3 fatigue

  • Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection

  • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.

  1. Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.

  2. Age ≥ 18 years

  3. Performance Status 0 - 1.

  4. No HIV disease. Due to alterations in host immunity, patients known to have HIV infection may not be enrolled.

  5. Non-pregnant and non-nursing. Due to the unknown teratogenic potential of chemotherapy, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.

  6. Required Initial Laboratory Values:

  • Creatinine ≤ 1.5 x upper limit of normal

Eligibility Criteria for Registration (to Low-Risk Cohort or High-Risk Cohort Randomization between Early Intervention Versus Observation with Later Treatment)

  1. Successful determination of IgVH mutational status by reference laboratory.

  2. Absence of progression of CLL, i.e., absence of the following:

  • Progressive splenomegaly and/or lymphadenopathy on two independent measures spaced two weeks apart. If one assessment notes progression, this should be repeated prior to re-registration.

  • Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/μL).

  • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.

  • Symptoms referable to CLL, including weight loss > 10% over the preceding 6 month period; grade 2 or 3 fatigue; or fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection.

  1. Required Laboratory Value:
  • Creatinine ≤ 1.5 x upper limit of normal

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Regional Medical CenterAnnistonAlabamaUnited States36202
2Clearview Cancer InstituteHuntsvilleAlabamaUnited States35805
3Sparks Regional Medical CenterFort SmithArkansasUnited States72901
4Providence Saint Joseph Medical Center - BurbankBurbankCaliforniaUnited States91505
5Virginia K. Crosson Cancer Center at St. Jude Medical CenterFullertonCaliforniaUnited States92835
6Memorial Medical CenterModestoCaliforniaUnited States95355
7Camino Medical Group - Treatment CenterMountain ViewCaliforniaUnited States94040
8Palo Alto Medical FoundationPalo AltoCaliforniaUnited States94301
9University of California Davis Cancer CenterSacramentoCaliforniaUnited States95817
10Kaiser Permanente Medical Office -Vandever Medical OfficeSan DiegoCaliforniaUnited States92120
11Aurora Presbyterian HospitalAuroraColoradoUnited States80012
12Boulder Community HospitalBoulderColoradoUnited States80301-9019
13Penrose Cancer Center at Penrose HospitalColorado SpringsColoradoUnited States80933
14St. Anthony Central HospitalDenverColoradoUnited States80204
15Porter Adventist HospitalDenverColoradoUnited States80210
16Presbyterian - St. Luke's Medical CenterDenverColoradoUnited States80218
17St. Joseph HospitalDenverColoradoUnited States80218
18Rose Medical CenterDenverColoradoUnited States80220
19CCOP - Colorado Cancer Research ProgramDenverColoradoUnited States80224-2522
20Swedish Medical CenterEnglewoodColoradoUnited States80110
21St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand JunctionColoradoUnited States81502
22North Colorado Medical CenterGreeleyColoradoUnited States80631
23Sky Ridge Medical CenterLone TreeColoradoUnited States80124
24Hope Cancer Care Center at Longmont United HospitalLongmontColoradoUnited States80501
25McKee Medical CenterLovelandColoradoUnited States80539
26St. Mary - Corwin Regional Medical CenterPuebloColoradoUnited States81004
27North Suburban Medical CenterThorntonColoradoUnited States80229
28Exempla Lutheran Medical CenterWheat RidgeColoradoUnited States80033
29Manchester Memorial HospitalManchesterConnecticutUnited States06040
30Tunnell Cancer Center at Beebe Medical CenterLewesDelawareUnited States19958
31CCOP - Christiana Care Health ServicesNewarkDelawareUnited States19713
32Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashingtonDistrict of ColumbiaUnited States20007
33Walter Reed Army Medical CenterWashingtonDistrict of ColumbiaUnited States20307-5001
34Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort LauderdaleFloridaUnited States33308
35Memorial Cancer Institute at Memorial Regional HospitalHollywoodFloridaUnited States33021
36Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiterFloridaUnited States33458
37CCOP - Mount Sinai Medical CenterMiami BeachFloridaUnited States33140
38Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlandoFloridaUnited States32803-1273
39M.D. Anderson Cancer Center at OrlandoOrlandoFloridaUnited States32806
40Sacred Heart Cancer Center at Sacred Heart HospitalPensacolaFloridaUnited States32504
41West Florida Cancer Institute at West Florida Hospital - PensacolaPensacolaFloridaUnited States32514
42Phoebe Cancer Center at Phoebe Putney Memorial HospitalAlbanyGeorgiaUnited States31701
43John B. Amos Cancer CenterColumbusGeorgiaUnited States31904
44Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoiseIdahoUnited States83712
45Saint Anthony's Hospital at Saint Anthony's Health CenterAltonIllinoisUnited States62002
46Hematology Oncology Associates of Illinois - BerwynBerwynIllinoisUnited States60402
47Illinois CancerCare - BloomingtonBloomingtonIllinoisUnited States61701
48St. Joseph Medical CenterBloomingtonIllinoisUnited States61701
49Illinois CancerCare - CantonCantonIllinoisUnited States61520
50Illinois CancerCare - CarthageCarthageIllinoisUnited States62321
51Memorial HospitalCarthageIllinoisUnited States62321
52Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicagoIllinoisUnited States60611-3013
53Hematology and Oncology AssociatesChicagoIllinoisUnited States60611
54Rush University Medical CenterChicagoIllinoisUnited States60612
55University of Chicago Cancer Research CenterChicagoIllinoisUnited States60637-1470
56Elmhurst Memorial HospitalElmhurstIllinoisUnited States60126
57Eureka Community HospitalEurekaIllinoisUnited States61530
58Illinois CancerCare - EurekaEurekaIllinoisUnited States61530
59Galesburg Clinic, PCGalesburgIllinoisUnited States61401
60Galesburg Cottage HospitalGalesburgIllinoisUnited States61401
61Illinois CancerCare - GalesburgGalesburgIllinoisUnited States61401
62Illinois CancerCare - HavanaHavanaIllinoisUnited States62644
63Mason District HospitalHavanaIllinoisUnited States62644
64Kellogg Cancer Care CenterHighland ParkIllinoisUnited States60035
65Midwest Center for Hematology/OncologyJolietIllinoisUnited States60432
66Illinois CancerCare - Kewanee ClinicKewaneeIllinoisUnited States61443
67North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyvilleIllinoisUnited States60048
68Illinois CancerCare - MacombMacombIllinoisUnited States61455
69McDonough District HospitalMacombIllinoisUnited States61455
70Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywoodIllinoisUnited States60153
71Trinity Cancer Center at Trinity Medical Center - 7th Street CampusMolineIllinoisUnited States61265
72MolineIllinoisUnited States61265
73Illinois CancerCare - MonmouthMonmouthIllinoisUnited States61462
74OSF Holy Family Medical CenterMonmouthIllinoisUnited States61462
75Good Samaritan Regional Health CenterMount VernonIllinoisUnited States62864
76Edward Hospital Cancer CenterNapervilleIllinoisUnited States60540
77La Grange Oncology Associates - GenevaNapervilleIllinoisUnited States60563
78Cancer Care and Hematology Specialists of Chicagoland - NilesNilesIllinoisUnited States60714
79BroMenn Regional Medical CenterNormalIllinoisUnited States61761
80Community Cancer CenterNormalIllinoisUnited States61761
81Illinois CancerCare - Community Cancer CenterNormalIllinoisUnited States61761
82Community Hospital of OttawaOttawaIllinoisUnited States61350
83Oncology Hematology Associates of Central Illinois, PC - OttawaOttawaIllinoisUnited States61350
84Cancer Treatment Center at Pekin HospitalPekinIllinoisUnited States61554
85Illinois CancerCare - PekinPekinIllinoisUnited States61603
86Proctor HospitalPeoriaIllinoisUnited States61614
87CCOP - Illinois Oncology Research AssociationPeoriaIllinoisUnited States61615
88Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoriaIllinoisUnited States61615
89Methodist Medical Center of IllinoisPeoriaIllinoisUnited States61636
90OSF St. Francis Medical CenterPeoriaIllinoisUnited States61637
91Illinois CancerCare - PeruPeruIllinoisUnited States61354
92Illinois Valley Community HospitalPeruIllinoisUnited States61354
93Illinois CancerCare - PrincetonPrincetonIllinoisUnited States61356
94Perry Memorial HospitalPrincetonIllinoisUnited States61356
95Swedish-American Regional Cancer CenterRockfordIllinoisUnited States61104-2315
96Hematology Oncology Associates - SkokieSkokieIllinoisUnited States60076
97Illinois CancerCare - Spring ValleySpring ValleyIllinoisUnited States61362
98St. Margaret's HospitalSpring ValleyIllinoisUnited States61362
99Central Dupage Cancer CenterWinfieldIllinoisUnited States60190
100St. Francis Hospital and Health Centers - Beech Grove CampusBeech GroveIndianaUnited States46107
101Community HospitalMunsterIndianaUnited States46321
102Reid Hospital & Health Care ServicesRichmondIndianaUnited States47374
103McFarland Clinic, PCAmesIowaUnited States50010
104Hematology Oncology Associates of the Quad CitiesBettendorfIowaUnited States52722
105BettendorfIowaUnited States52722
106Medical Oncology and Hematology Associates - West Des MoinesCliveIowaUnited States50325
107Genesis Regional Cancer Center at Genesis Medical CenterDavenportIowaUnited States52803
108Genesis Medical Center - West CampusDavenportIowaUnited States52804
109Mercy Capitol HospitalDes MoinesIowaUnited States50307
110CCOP - Iowa Oncology Research AssociationDes MoinesIowaUnited States50309
111John Stoddard Cancer Center at Iowa Methodist Medical CenterDes MoinesIowaUnited States50309
112Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes MoinesIowaUnited States50309
113Medical Oncology and Hematology Associates at Mercy Cancer CenterDes MoinesIowaUnited States50314
114Mercy Cancer Center at Mercy Medical Center - Des MoinesDes MoinesIowaUnited States50314
115John Stoddard Cancer Center at Iowa Lutheran HospitalDes MoinesIowaUnited States50316
116Holden Comprehensive Cancer Center at University of IowaIowa CityIowaUnited States52242-1002
117Veterans Affairs Medical Center - Iowa CityIowa CityIowaUnited States52246
118Siouxland Hematology-Oncology Associates, LLPSioux CityIowaUnited States51101
119Mercy Medical Center - Sioux CitySioux CityIowaUnited States51104
120St. Luke's Regional Medical CenterSioux CityIowaUnited States51104
121Cedar Valley Medical Specialists, PC - West Ridgeway AvenueWaterlooIowaUnited States50701
122Covenant Cancer Treatment CenterWaterlooIowaUnited States50702
123Cancer Center of Kansas, PA - ChanuteChanuteKansasUnited States66720
124Cancer Center of Kansas, PA - Dodge CityDodge CityKansasUnited States67801
125Cancer Center of Kansas, PA - El DoradoEl DoradoKansasUnited States67042
126Cancer Center of Kansas - Fort ScottFort ScottKansasUnited States66701
127Cancer Center of Kansas-IndependenceIndependenceKansasUnited States67301
128Cancer Center of Kansas, PA - KingmanKingmanKansasUnited States67068
129Lawrence Memorial HospitalLawrenceKansasUnited States66044
130Southwest Medical CenterLiberalKansasUnited States67901
131Cancer Center of Kansas, PA - NewtonNewtonKansasUnited States67114
132Menorah Medical CenterOverland ParkKansasUnited States66209
133Saint Luke's Hospital - SouthOverland ParkKansasUnited States66213
134Cancer Center of Kansas, PA - ParsonsParsonsKansasUnited States67357
135Cancer Center of Kansas, PA - PrattPrattKansasUnited States67124
136Cancer Center of Kansas, PA - SalinaSalinaKansasUnited States67042
137Shawnee Mission Medical CenterShawnee MissionKansasUnited States66204
138Cotton-O'Neil Cancer CenterTopekaKansasUnited States66606
139Cancer Center of Kansas, PA - WellingtonWellingtonKansasUnited States67152
140Associates in Womens Health, PA - North ReviewWichitaKansasUnited States67208
141Cancer Center of Kansas, PA - Medical Arts TowerWichitaKansasUnited States67208
142Cancer Center of Kansas, PA - WichitaWichitaKansasUnited States67214
143CCOP - WichitaWichitaKansasUnited States67214
144Via Christi Cancer Center at Via Christi Regional Medical CenterWichitaKansasUnited States67214
145Wesley Medical CenterWichitaKansasUnited States67214
146Cancer Center of Kansas, PA - WinfieldWinfieldKansasUnited States67156
147CancerCare of Maine at Eastern Maine Medical CenterBangorMaineUnited States04401
148MaineGeneral Medical Center - WatervilleWatervilleMaineUnited States04901
149Greenebaum Cancer Center at University of Maryland Medical CenterBaltimoreMarylandUnited States21201
150Union Hospital Cancer Program at Union HospitalElktonMarylandUnited States21921
151Massachusetts General HospitalBostonMassachusettsUnited States02114
152Dana-Farber/Brigham and Women's Cancer CenterBostonMassachusettsUnited States02115
153Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
154Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
155Lahey Clinic Medical Center - BurlingtonBurlingtonMassachusettsUnited States01805
156Hickman Cancer Center at Bixby Medical CenterAdrianMichiganUnited States49221
157Saint Joseph Mercy Cancer CenterAnn ArborMichiganUnited States48106-0995
158CCOP - Michigan Cancer Research ConsortiumAnn ArborMichiganUnited States48106
159Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearbornMichiganUnited States48123-2500
160Green Bay Oncology, Limited - EscanabaEscanabaMichiganUnited States49431
161Genesys Hurley Cancer InstituteFlintMichiganUnited States48503
162Hurley Medical CenterFlintMichiganUnited States48503
163Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe WoodsMichiganUnited States48236
164Dickinson County Healthcare SystemIron MountainMichiganUnited States49801
165Foote Memorial HospitalJacksonMichiganUnited States49201
166Borgess Medical CenterKalamazooMichiganUnited States49001
167West Michigan Cancer CenterKalamazooMichiganUnited States49007-3731
168Bronson Methodist HospitalKalamazooMichiganUnited States49007
169Haematology-Oncology Associates of Ohio and Michigan, PCLambertvilleMichiganUnited States48144
170Sparrow Regional Cancer CenterLansingMichiganUnited States48912-1811
171St. Mary Mercy HospitalLivoniaMichiganUnited States48154
172Community Cancer Center of MonroeMonroeMichiganUnited States48162
173Mercy Memorial Hospital - MonroeMonroeMichiganUnited States48162
174St. Joseph Mercy OaklandPontiacMichiganUnited States48341-2985
175Mercy Regional Cancer Center at Mercy HospitalPort HuronMichiganUnited States48060
176Seton Cancer Institute at Saint Mary's - SaginawSaginawMichiganUnited States48601
177Oncology Care Associates, PLLCSaint JosephMichiganUnited States49085
178Providence Cancer Institute at Providence Hospital - Southfield CampusSouthfieldMichiganUnited States48075
179St. John Macomb HospitalWarrenMichiganUnited States48093
180AlexandriaMinnesotaUnited States56308
181Fairview Ridges HospitalBurnsvilleMinnesotaUnited States55337
182Mercy and Unity Cancer Center at Mercy HospitalCoon RapidsMinnesotaUnited States55433
183Fairview Southdale HospitalEdinaMinnesotaUnited States55435
184Mercy and Unity Cancer Center at Unity HospitalFridleyMinnesotaUnited States55432
185Hutchinson Area Health CareHutchinsonMinnesotaUnited States55350
186HealthEast Cancer Care at St. John's HospitalMaplewoodMinnesotaUnited States55109
187Minnesota Oncology Hematology, PA - MaplewoodMaplewoodMinnesotaUnited States55109
188Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolisMinnesotaUnited States55407
189Hennepin County Medical Center - MinneapolisMinneapolisMinnesotaUnited States55415
190Veterans Affairs Medical Center - MinneapolisMinneapolisMinnesotaUnited States55417
191Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdaleMinnesotaUnited States55422-2900
192Mayo Clinic Cancer CenterRochesterMinnesotaUnited States55905
193CentraCare Clinic - River CampusSaint CloudMinnesotaUnited States56303
194Coborn Cancer CenterSaint CloudMinnesotaUnited States56303
195CCOP - Metro-MinnesotaSaint Louis ParkMinnesotaUnited States55416
196Park Nicollet Cancer CenterSaint Louis ParkMinnesotaUnited States55416
197Regions Hospital Cancer Care CenterSaint PaulMinnesotaUnited States55101
198United HospitalSaint PaulMinnesotaUnited States55102
199St. Francis Cancer Center at St. Francis Medical CenterShakopeeMinnesotaUnited States55379
200Ridgeview Medical CenterWaconiaMinnesotaUnited States55387
201Minnesota Oncology Hematology, PA - WoodburyWoodburyMinnesotaUnited States55125
202Saint Francis Medical CenterCape GirardeauMissouriUnited States63703
203Truman Medical Center - Hospital HillKansas CityMissouriUnited States64108
204Saint Luke's Cancer Institute at Saint Luke's HospitalKansas CityMissouriUnited States64111
205St. Joseph Medical CenterKansas CityMissouriUnited States64114
206North Kansas City HospitalKansas CityMissouriUnited States64116
207Parvin Radiation OncologyKansas CityMissouriUnited States64116
208CCOP - Kansas CityKansas CityMissouriUnited States64131
209Research Medical CenterKansas CityMissouriUnited States64132
210Saint Luke's East - Lee's SummitLee's SummitMissouriUnited States64086
211Liberty HospitalLibertyMissouriUnited States64068
212Heartland Regional Medical CenterSaint JosephMissouriUnited States64506
213Midwest Hematology Oncology Group, IncorporatedSaint LouisMissouriUnited States63109
214Saint Louis University Cancer CenterSaint LouisMissouriUnited States63110
215Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSaint LouisMissouriUnited States63110
216CCOP - St. Louis-Cape GirardeauSaint LouisMissouriUnited States63141
217David C. Pratt Cancer Center at St. John's MercySaint LouisMissouriUnited States63141
218CCOP - Cancer Research for the OzarksSpringfieldMissouriUnited States65802
219St. John's Regional Health CenterSpringfieldMissouriUnited States65804
220Hulston Cancer Center at Cox Medical Center SouthSpringfieldMissouriUnited States65807
221CCOP - Montana Cancer ConsortiumBillingsMontanaUnited States59101
222Hematology-Oncology Centers of the Northern Rockies - BillingsBillingsMontanaUnited States59101
223Northern Rockies Radiation Oncology CenterBillingsMontanaUnited States59101
224St. Vincent Healthcare Cancer Care ServicesBillingsMontanaUnited States59101
225Billings Clinic - DowntownBillingsMontanaUnited States59107-7000
226Bozeman Deaconess Cancer CenterBozemanMontanaUnited States59715
227St. James Healthcare Cancer CareButteMontanaUnited States59701
228Big Sky OncologyGreat FallsMontanaUnited States59405-5309
229Great Falls Clinic - Main FacilityGreat FallsMontanaUnited States59405
230Sletten Cancer Institute at Benefis HealthcareGreat FallsMontanaUnited States59405
231Great FallsMontanaUnited States59405
232Northern Montana HospitalHavreMontanaUnited States59501
233St. Peter's HospitalHelenaMontanaUnited States59601
234Glacier Oncology, PLLCKalispellMontanaUnited States59901
235Kalispell Medical Oncology at KRMCKalispellMontanaUnited States59901
236Kalispell Regional Medical CenterKalispellMontanaUnited States59901
237Community Medical CenterMissoulaMontanaUnited States59801
238Guardian Oncology and Center for WellnessMissoulaMontanaUnited States59804
239Montana Cancer Specialists at Montana Cancer CenterMissoulaMontanaUnited States59807-7877
240Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoulaMontanaUnited States59807
241CCOP - Missouri Valley Cancer ConsortiumOmahaNebraskaUnited States68106
242Methodist Estabrook Cancer CenterOmahaNebraskaUnited States68114
243Immanuel Medical CenterOmahaNebraskaUnited States68122
244Alegant Health Cancer Center at Bergan Mercy Medical CenterOmahaNebraskaUnited States68124
245Creighton University Medical CenterOmahaNebraskaUnited States68131-2197
246Veterans Affairs Medical Center - East OrangeEast OrangeNew JerseyUnited States07018-1095
247Hunterdon Regional Cancer Center at Hunterdon Medical CenterFlemingtonNew JerseyUnited States08822
248Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital MarltonMarltonNew JerseyUnited States08053
249Cancer Institute of New Jersey at Cooper - VoorheesVoorheesNew JerseyUnited States08043
250Fox Chase Virtua Health Cancer Program at Virtua West JerseyVoorheesNew JerseyUnited States08043
251University of New Mexico Cancer CenterAlbuquerqueNew MexicoUnited States87131-5636
252New Mexico Cancer Care AssociatesSanta FeNew MexicoUnited States87505
253CCOP - Hematology-Oncology Associates of Central New YorkEast SyracuseNew YorkUnited States13057
254Adirondack Cancer Care - Glens FallsGlens FallsNew YorkUnited States12801
255Monter Cancer Center of the North Shore-LIJ Health SystemLake SuccessNew YorkUnited States11042
256CCOP - North Shore University HospitalManhassetNew YorkUnited States11030
257Don Monti Comprehensive Cancer Center at North Shore University HospitalManhassetNew YorkUnited States11030
258Long Island Jewish Medical CenterNew Hyde ParkNew YorkUnited States11040
259New York Weill Cornell Cancer Center at Cornell UniversityNew YorkNew YorkUnited States10021
260James P. Wilmot Cancer Center at University of Rochester Medical CenterRochesterNew YorkUnited States14642
261Stony Brook University Cancer CenterStony BrookNew YorkUnited States11794-9446
262SUNY Upstate Medical University HospitalSyracuseNew YorkUnited States13210
263Veterans Affairs Medical Center - SyracuseSyracuseNew YorkUnited States13210
264Mission Hospitals - Memorial CampusAshevilleNorth CarolinaUnited States28801
265Batte Cancer Center at Northeast Medical CenterConcordNorth CarolinaUnited States28025
266Wayne Memorial Hospital, IncorporatedGoldsboroNorth CarolinaUnited States27534
267Pardee Memorial HospitalHendersonvilleNorth CarolinaUnited States28791
268Kinston Medical SpecialistsKinstonNorth CarolinaUnited States28501
269Wake Forest University Comprehensive Cancer CenterWinston-SalemNorth CarolinaUnited States27157-1096
270Bismarck Cancer CenterBismarckNorth DakotaUnited States58501
271Medcenter One Hospital Cancer Care CenterBismarckNorth DakotaUnited States58501
272Mid Dakota Clinic, PCBismarckNorth DakotaUnited States58501
273St. Alexius Medical Center Cancer CenterBismarckNorth DakotaUnited States58502
274Summa Center for Cancer Care at Akron City HospitalAkronOhioUnited States44309-2090
275Mary Rutan HospitalBellefontaineOhioUnited States43311
276Wood County Oncology CenterBowling GreenOhioUnited States43402
277Adena Regional Medical CenterChillicotheOhioUnited States45601
278MetroHealth Cancer Care Center at MetroHealth Medical CenterClevelandOhioUnited States44109
279North Coast Cancer Care - ClydeClydeOhioUnited States43410
280Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbusOhioUnited States43210-1240
281Riverside Methodist Hospital Cancer CareColumbusOhioUnited States43214-3998
282CCOP - ColumbusColumbusOhioUnited States43215
283Grant Medical Center Cancer CareColumbusOhioUnited States43215
284Mount Carmel Health - West HospitalColumbusOhioUnited States43222
285Doctors Hospital at Ohio HealthColumbusOhioUnited States43228
286Grandview HospitalDaytonOhioUnited States45405
287Good Samaritan HospitalDaytonOhioUnited States45406
288David L. Rike Cancer Center at Miami Valley HospitalDaytonOhioUnited States45409
289Samaritan North Cancer Care CenterDaytonOhioUnited States45415
290CCOP - DaytonDaytonOhioUnited States45420
291Grady Memorial HospitalDelawareOhioUnited States43015
292Hematology Oncology CenterElyriaOhioUnited States44035
293Blanchard Valley Medical AssociatesFindlayOhioUnited States45840
294Middletown Regional HospitalFranklinOhioUnited States45005-1066
295Wayne HospitalGreenvilleOhioUnited States45331
296Charles F. Kettering Memorial HospitalKetteringOhioUnited States45429
297Fairfield Medical CenterLancasterOhioUnited States43130
298St. Rita's Medical CenterLimaOhioUnited States45801
299Lima Memorial HospitalLimaOhioUnited States45804
300Strecker Cancer Center at Marietta Memorial HospitalMariettaOhioUnited States45750
301Northwest Ohio Oncology CenterMaumeeOhioUnited States43537-1839
302St. Luke's HospitalMaumeeOhioUnited States43537
303Licking Memorial Cancer Care Program at Licking Memorial HospitalNewarkOhioUnited States43055
304St. Charles Mercy HospitalOregonOhioUnited States43616
305Toledo Clinic - OregonOregonOhioUnited States43616
306North Coast Cancer Care, IncorporatedSanduskyOhioUnited States44870
307Mercy Medical CenterSpringfieldOhioUnited States45504
308Community Hospital of Springfield and Clark CountySpringfieldOhioUnited States45505
309Flower Hospital Cancer CenterSylvaniaOhioUnited States43560
310Mercy Hospital of TiffinTiffinOhioUnited States44883
311Toledo HospitalToledoOhioUnited States43606
312St. Vincent Mercy Medical CenterToledoOhioUnited States43608
313Medical University of Ohio Cancer CenterToledoOhioUnited States43614
314CCOP - Toledo Community HospitalToledoOhioUnited States43617
315St. Anne Mercy HospitalToledoOhioUnited States43623
316Toledo Clinic, Incorporated - Main ClinicToledoOhioUnited States43623
317UVMC Cancer Care Center at Upper Valley Medical CenterTroyOhioUnited States45373-1300
318Fulton County Health CenterWauseonOhioUnited States43567
319Mount Carmel St. Ann's Cancer CenterWestervilleOhioUnited States43081
320Clinton Memorial HospitalWilmingtonOhioUnited States45177
321Ruth G. McMillan Cancer Center at Greene Memorial HospitalXeniaOhioUnited States45385
322Genesis - Good Samaritan HospitalZanesvilleOhioUnited States43701
323Providence Milwaukie HospitalMilwaukieOregonUnited States97222
324Providence Cancer Center at Providence Portland Medical CenterPortlandOregonUnited States97213-2967
325CCOP - Columbia River Oncology ProgramPortlandOregonUnited States97225
326Providence St. Vincent Medical CenterPortlandOregonUnited States97225
327Kaiser Permanente Health Care - PortlandPortlandOregonUnited States97232
328Legacy Meridian Park HospitalTualatinOregonUnited States97062
329Geisinger Cancer Institute at Geisinger HealthDanvillePennsylvaniaUnited States17822-0001
330Geisinger Hazleton Cancer CenterHazletonPennsylvaniaUnited States18201
331Riddle Memorial Hospital Cancer CenterMediaPennsylvaniaUnited States19063
332Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphiaPennsylvaniaUnited States19107-5541
333Joan Karnell Cancer Center at Pennsylvania HospitalPhiladelphiaPennsylvaniaUnited States19107
334Cancer Center at Phoenixville HospitalPhoenixvillePennsylvaniaUnited States19460
335Geisinger Medical Group - Scenery ParkState CollegePennsylvaniaUnited States16801
336Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-BarrePennsylvaniaUnited States18711
337Memorial Hospital of Rhode IslandPawtucketRhode IslandUnited States02860
338Hollings Cancer Center at Medical University of South CarolinaCharlestonSouth CarolinaUnited States29425
339McLeod Regional Medical CenterFlorenceSouth CarolinaUnited States29501
340CCOP - GreenvilleGreenvilleSouth CarolinaUnited States29615
341Mountainview MedicalBerlinVermontUnited States05602
342Fletcher Allen Health Care - University Health Center CampusBurlingtonVermontUnited States05401
343Fredericksburg Oncology, IncorporatedFredericksburgVirginiaUnited States22401
344St. Joseph Cancer CenterBellinghamWashingtonUnited States98225
345Olympic Hematology and OncologyBremertonWashingtonUnited States98310
346Columbia Basin HematologyKennewickWashingtonUnited States99336
347Harrison Poulsbo Hematology and OnocologyPoulsboWashingtonUnited States98370
348Minor and James Medical, PLLCSeattleWashingtonUnited States98104
349Group Health Central HospitalSeattleWashingtonUnited States98112
350Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattleWashingtonUnited States98122-4307
351Polyclinic First HillSeattleWashingtonUnited States98122
352University Cancer Center at University of Washington Medical CenterSeattleWashingtonUnited States98195-6043
353Cancer Care Northwest - Spokane SouthSpokaneWashingtonUnited States99202
354Evergreen Hematology and Oncology, PSSpokaneWashingtonUnited States99218
355Southwest Washington Medical Center Cancer CenterVancouverWashingtonUnited States98668
356Marshfield Clinic - Chippewa CenterChippewa FallsWisconsinUnited States54729
357Marshfield Clinic Cancer Care at Regional Cancer CenterEau ClaireWisconsinUnited States54701
358Central Wisconsin Cancer Program at Agnesian HealthCareFond Du LacWisconsinUnited States54935
359Oncology Alliance, SC - Milwaukee - EastGlendaleWisconsinUnited States53212-1038
360Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen BayWisconsinUnited States54301-3526
361Green Bay Oncology, Limited at St. Mary's HospitalGreen BayWisconsinUnited States54303
362St. Mary's Hospital Medical Center - Green BayGreen BayWisconsinUnited States54303
363St. Vincent Hospital Regional Cancer CenterGreen BayWisconsinUnited States54307-3508
364Holy Family Memorial Medical Center Cancer Care CenterManitowocWisconsinUnited States54221-1450
365Bay Area Cancer Care Center at Bay Area Medical CenterMarinetteWisconsinUnited States54143
366Marshfield Clinic - Marshfield CenterMarshfieldWisconsinUnited States54449
367Saint Joseph's HospitalMarshfieldWisconsinUnited States54449
368Marshfield Clinic - Lakeland CenterMinocquaWisconsinUnited States54548
369Regional Cancer Center at Oconomowoc Memorial HospitalOconomowocWisconsinUnited States53066
370Green Bay Oncology, Limited - Oconto FallsOconto FallsWisconsinUnited States54154
371Ministry Medical Group at Saint Mary's HospitalRhinelanderWisconsinUnited States54501
372Marshfield Clinic - Indianhead CenterRice LakeWisconsinUnited States54868
373Vince Lombardi Cancer Clinic - SheboyganSheboyganWisconsinUnited States53081
374Saint Michael's Hospital Cancer CenterStevens PointWisconsinUnited States54481
375Green Bay Oncology, Limited - Sturgeon BaySturgeon BayWisconsinUnited States54235
376Waukesha Memorial Hospital Regional Cancer CenterWaukeshaWisconsinUnited States53188
377Marshfield Clinic - Weston CenterWestonWisconsinUnited States54476
378Marshfield Clinic - Wisconsin Rapids CenterWisconsin RapidsWisconsinUnited States54494
379Welch Cancer Center at Sheridan Memorial HospitalSheridanWyomingUnited States82801
380CancerCare ManitobaWinnipegManitobaCanadaR3E 0V9
381Moncton HospitalMonctonNew BrunswickCanadaE1C 6Z8
382Nova Scotia Cancer CentreHalifaxNova ScotiaCanadaB3H 1V8
383Margaret and Charles Juravinski Cancer CentreHamiltonOntarioCanadaL8V 5C2
384Northeastern Ontario Regional Cancer CentreSudburyOntarioCanadaP3E 5J1
385Edmond Odette Cancer Centre at SunnybrookTorontoOntarioCanadaM4N 3M5
386Maisonneuve-Rosemont HospitalMontrealQuebecCanadaH1T 2M4
387Allan Blair Cancer Centre at Pasqua HospitalReginaSaskatchewanCanadaS4T 7T1

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: John C. Byrd, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00513747
Other Study ID Numbers:
  • CALGB-10501
  • U10CA031946
  • CDR0000537685
First Posted:
Aug 9, 2007
Last Update Posted:
Apr 22, 2020
Last Verified:
Apr 1, 2020

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailThe Enrollment number in the Protocol Section does not match the number of participants who started in the Participant Flow due to limited data on one participant (i.e. the participant was registered but was not randomized or classified (high vs. low risk) because the participant withdrew consent for all follow-up the same day of registration).
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later Treatment
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13, > 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Patients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Period Title: Overall Study
STARTED171155
Received at Least One Dose of Treatment91140
COMPLETED171155
NOT COMPLETED000

Baseline Characteristics

Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later TreatmentTotal
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13,> 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Patients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Total of all reporting groups
Overall Participants17115583
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
60
60
59
60
Sex: Female, Male (Count of Participants)
Female
1
5.9%
3
27.3%
23
41.8%
27
32.5%
Male
16
94.1%
8
72.7%
32
58.2%
56
67.5%

Outcome Measures

1. Primary Outcome
TitleTime to Second Treatment in High Risk Patients
DescriptionKaplan-Meier analysis was conducted to estimate the distribution of time from randomization to second treatment or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.
Time FrameUp to 72 months

Outcome Measure Data

Analysis Population Description
Randomized High Risk patients are included in this analysis.
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later Treatment
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13,> 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Measure Participants1711
Median (95% Confidence Interval) [months]
62.7
56.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: High Risk Early Intervention, Arm B: High Risk Observation + Later Treatment
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.1521
Comments
MethodLog Rank
Comments
2. Primary Outcome
TitleDisease-Free Survival in High Risk Patients
DescriptionKaplan-Meier analysis was conducted to estimate disease free survival defined as:> Arm A: Time from randomization until Second Treatment (first relapse) or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.> Arm B: Time from randomization until First Treatment (first relapse) or death whichever comes first. Events were defined as the start of first treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.
Time FrameUp to 72 months

Outcome Measure Data

Analysis Population Description
Randomized High Risk patients are included in this analysis.
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later Treatment
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13,> 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Measure Participants1711
Median (95% Confidence Interval) [months]
62.7
39.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: High Risk Early Intervention, Arm B: High Risk Observation + Later Treatment
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.0097
Comments
MethodLog Rank
Comments
3. Primary Outcome
TitleOverall Survival (OS) for High Risk Patients
DescriptionKaplan-Meier analysis was conducted to estimate the distribution of time from randomization to death from any cause. Estimates were not stratified. Patients who did not experience this primary outcome had their survival times censored at their last follow-up.
Time FrameUp to 72 months

Outcome Measure Data

Analysis Population Description
Randomized High Risk patients are included in this analysis.
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later Treatment
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13,> 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Measure Participants1711
Median (95% Confidence Interval) [months]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: High Risk Early Intervention, Arm B: High Risk Observation + Later Treatment
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.4645
Comments
MethodLog Rank
Comments
4. Secondary Outcome
TitleNumber of Patients With Mutated and Unmutated IgVH Genes
DescriptionNumber of patients with mutated and unmutated IgVH genes are reported below.
Time FrameOnce at baseline

Outcome Measure Data

Analysis Population Description
All patients are included in this analysis.
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later TreatmentTotal
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13,> 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Patients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Arm A + Arm B + Arm C patients
Measure Participants17115583
Unmutated
17
100%
11
100%
0
0%
28
33.7%
Mutated
0
0%
0
0%
55
100%
55
66.3%
5. Secondary Outcome
TitleOverall Survival in Low Risk Patients
DescriptionOverall survival in low risk patients (registration to first treatment or death)> • Events were defined as death from any cause. Low risk Patients who were alive were censored at their last known follow-up.
Time FrameUp to 72 months

Outcome Measure Data

Analysis Population Description
Low Risk patients are included in this analysis.
Arm/Group TitleArm C: Low Risk Observation + Later Treatment
Arm/Group DescriptionPatients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Measure Participants55
Median (95% Confidence Interval) [months]
58.1
6. Secondary Outcome
TitleTime to First Treatment Survival in Low Risk Patients
DescriptionTime to First Treatment Survival in low risk patients (registration to first treatment or death)> • Events were defined as the start of first treatment or death from any cause. Patients who didn't receive their first treatment were censored at their last known follow-up.
Time FrameUp to 72 months

Outcome Measure Data

Analysis Population Description
Low Risk patients are included in this analysis.
Arm/Group TitleArm C: Low Risk Observation + Later Treatment
Arm/Group DescriptionPatients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Measure Participants55
Median (95% Confidence Interval) [months]
58.1

Adverse Events

Time FrameUp to 72 months
Adverse Event Reporting Description Participants who received at least one dose of treatment are evaluable for adverse events (AEs) (i.e. summarized in the Serious and Other(Not Including Serious) AEs tables). All participants are followed for their survival status (i.e. summarized in the All-Cause Mortality table).
Arm/Group TitleArm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later Treatment
Arm/Group DescriptionRandomized Patients receive 50, 325, and 375 mg/m^2 rituximab IV over 4 hours on days 1, 3, and 5 of week 1, respectively; then patients receive 375 mg/m^2 rituximab IV on day 1 of weeks 5, 9, 13, > 17, and 21. Patients also receive 25 mg/m^2/day fludarabine monophosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.Randomized Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.Patients who were registered to the low-risk arm may elect to provide continued follow-up information on their treatment, disease course, and outcome regardless of the medical therapy they and their physician select. Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in Arm A. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
All Cause Mortality
Arm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/17 (5.9%) 2/11 (18.2%) 2/55 (3.6%)
Serious Adverse Events
Arm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/9 (0%) 0/11 (0%) 0/40 (0%)
Other (Not Including Serious) Adverse Events
Arm A: High Risk Early InterventionArm B: High Risk Observation + Later TreatmentArm C: Low Risk Observation + Later Treatment
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total9/9 (100%) 11/11 (100%) 40/40 (100%)
Blood and lymphatic system disorders
Blood disorder0/9 (0%) 01/11 (9.1%) 15/40 (12.5%) 17
Febrile neutropenia1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Hemoglobin decreased7/9 (77.8%) 255/11 (45.5%) 1616/40 (40%) 43
Cardiac disorders
Atrial fibrillation1/9 (11.1%) 20/11 (0%) 00/40 (0%) 0
Atrioventricular block first degree0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Myocardial ischemia1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Palpitations0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Ear and labyrinth disorders
External ear pain0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Hearing impaired0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Tinnitus0/9 (0%) 01/11 (9.1%) 30/40 (0%) 0
Gastrointestinal disorders
Abdominal pain0/9 (0%) 00/11 (0%) 02/40 (5%) 2
Constipation0/9 (0%) 01/11 (9.1%) 20/40 (0%) 0
Diarrhea1/9 (11.1%) 21/11 (9.1%) 12/40 (5%) 2
Dyspepsia0/9 (0%) 00/11 (0%) 01/40 (2.5%) 2
Dysphagia0/9 (0%) 00/11 (0%) 01/40 (2.5%) 3
Gastrointestinal disorder0/9 (0%) 00/11 (0%) 02/40 (5%) 2
Hemorrhoids0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Nausea4/9 (44.4%) 81/11 (9.1%) 12/40 (5%) 3
Tooth disorder0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Vomiting0/9 (0%) 00/11 (0%) 02/40 (5%) 2
General disorders
Chest pain1/9 (11.1%) 10/11 (0%) 02/40 (5%) 2
Chills0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Fatigue9/9 (100%) 329/11 (81.8%) 3019/40 (47.5%) 70
General symptom0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Pain0/9 (0%) 00/11 (0%) 03/40 (7.5%) 3
Hepatobiliary disorders
Cholecystitis0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Immune system disorders
Hypersensitivity1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Infections and infestations
Bladder infection(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Bronchitis(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Bronchitis(gr 3/4 ANC)0/9 (0%) 00/11 (0%) 02/40 (5%) 2
Gastric infection(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Gingival infection(gr 0/1/2 ANC)1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Infection(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Infectious colitis(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Infectious meningitis(gr 0/1/2 ANC)0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Laryngitis(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Lip infection(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Otitis externa(unknown ANC)0/9 (0%) 01/11 (9.1%) 21/40 (2.5%) 1
Pharyngitis(gr 3/4 ANC)1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Pneumonia(gr 0/1/2 ANC)1/9 (11.1%) 11/11 (9.1%) 11/40 (2.5%) 1
Rhinitis infective(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Sinusitis(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 06/40 (15%) 7
Sinusitis(unknown ANC)0/9 (0%) 00/11 (0%) 02/40 (5%) 3
Skin infection2/9 (22.2%) 20/11 (0%) 01/40 (2.5%) 1
Skin infection(gr 3/4 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Skin infection(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Soft tissue infection(gr 3/4 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Tooth infection(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Upper respiratory infection(gr 3/4 ANC)0/9 (0%) 01/11 (9.1%) 11/40 (2.5%) 1
Upper respiratory infection(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Upper respiratory infectn(gr 0/1/2 ANC)0/9 (0%) 00/11 (0%) 07/40 (17.5%) 7
Ureteritis(unknown ANC)0/9 (0%) 01/11 (9.1%) 31/40 (2.5%) 6
Urinary tract infection(gr 0/1/2 ANC)1/9 (11.1%) 10/11 (0%) 04/40 (10%) 5
Urinary tract infection(gr 3/4 ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Urinary tract infection(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Vaginal infection(unknown ANC)0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Injury, poisoning and procedural complications
Fracture0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Investigations
Alanine aminotransferase increased1/9 (11.1%) 10/11 (0%) 02/40 (5%) 2
Aspartate aminotransferase increased0/9 (0%) 01/11 (9.1%) 12/40 (5%) 2
Creatinine increased0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Laboratory test abnormal1/9 (11.1%) 10/11 (0%) 01/40 (2.5%) 1
Leukocyte count decreased4/9 (44.4%) 60/11 (0%) 01/40 (2.5%) 1
Lymphocyte count decreased4/9 (44.4%) 161/11 (9.1%) 11/40 (2.5%) 1
Neutrophil count decreased7/9 (77.8%) 212/11 (18.2%) 58/40 (20%) 22
Platelet count decreased5/9 (55.6%) 214/11 (36.4%) 1714/40 (35%) 55
Serum cholesterol increased0/9 (0%) 00/11 (0%) 02/40 (5%) 3
Weight gain1/9 (11.1%) 30/11 (0%) 00/40 (0%) 0
Weight loss0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Metabolism and nutrition disorders
Anorexia1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Blood glucose increased0/9 (0%) 03/11 (27.3%) 33/40 (7.5%) 11
Glucose intolerance0/9 (0%) 00/11 (0%) 01/40 (2.5%) 14
Serum albumin decreased0/9 (0%) 00/11 (0%) 02/40 (5%) 2
Serum calcium decreased0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Serum magnesium decreased0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Serum potassium decreased0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Serum potassium increased0/9 (0%) 01/11 (9.1%) 11/40 (2.5%) 1
Serum sodium decreased0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Musculoskeletal and connective tissue disorders
Arthralgia1/9 (11.1%) 20/11 (0%) 02/40 (5%) 3
Arthritis0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Back pain1/9 (11.1%) 41/11 (9.1%) 23/40 (7.5%) 5
Bone pain0/9 (0%) 00/11 (0%) 01/40 (2.5%) 2
Muscle weakness lower limb0/9 (0%) 01/11 (9.1%) 20/40 (0%) 0
Musculoskeletal disorder0/9 (0%) 00/11 (0%) 02/40 (5%) 4
Myalgia1/9 (11.1%) 10/11 (0%) 01/40 (2.5%) 1
Neck pain0/9 (0%) 01/11 (9.1%) 21/40 (2.5%) 1
Upper extremity dysfunction0/9 (0%) 00/11 (0%) 01/40 (2.5%) 2
Nervous system disorders
Dizziness0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Headache2/9 (22.2%) 21/11 (9.1%) 32/40 (5%) 4
Neuralgia0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Neurological disorder NOS0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Syncope0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Tremor0/9 (0%) 01/11 (9.1%) 20/40 (0%) 0
Psychiatric disorders
Anxiety0/9 (0%) 01/11 (9.1%) 21/40 (2.5%) 1
Confusion0/9 (0%) 00/11 (0%) 01/40 (2.5%) 4
Depression1/9 (11.1%) 14/11 (36.4%) 241/40 (2.5%) 1
Insomnia1/9 (11.1%) 32/11 (18.2%) 52/40 (5%) 2
Renal and urinary disorders
Bladder pain0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Urogenital disorder0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis1/9 (11.1%) 11/11 (9.1%) 12/40 (5%) 2
Bronchospasm1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Cough0/9 (0%) 02/11 (18.2%) 21/40 (2.5%) 1
Dyspnea1/9 (11.1%) 55/11 (45.5%) 145/40 (12.5%) 5
Hypoxia1/9 (11.1%) 10/11 (0%) 00/40 (0%) 0
Pharyngolaryngeal pain1/9 (11.1%) 10/11 (0%) 01/40 (2.5%) 2
Respiratory disorder0/9 (0%) 01/11 (9.1%) 20/40 (0%) 0
Sinus pain0/9 (0%) 00/11 (0%) 01/40 (2.5%) 3
Voice alteration0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Skin and subcutaneous tissue disorders
Erythema multiforme0/9 (0%) 01/11 (9.1%) 10/40 (0%) 0
Rash desquamating2/9 (22.2%) 62/11 (18.2%) 62/40 (5%) 2
Skin disorder0/9 (0%) 01/11 (9.1%) 23/40 (7.5%) 4
Skin ulceration0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1
Sweating0/9 (0%) 02/11 (18.2%) 31/40 (2.5%) 2
Vascular disorders
Hot flashes0/9 (0%) 01/11 (9.1%) 12/40 (5%) 4
Hypertension1/9 (11.1%) 10/11 (0%) 02/40 (5%) 2
Hypotension2/9 (22.2%) 20/11 (0%) 02/40 (5%) 2
Thrombosis0/9 (0%) 00/11 (0%) 01/40 (2.5%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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/TitleJohn Byrd, MD
OrganizationThe Arthur James Comprehensive Cancer Center
Phone614-293-9869
Emailjohn.byrd@osumc.edu
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00513747
Other Study ID Numbers:
  • CALGB-10501
  • U10CA031946
  • CDR0000537685
First Posted:
Aug 9, 2007
Last Update Posted:
Apr 22, 2020
Last Verified:
Apr 1, 2020