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A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With Previously Untreated Mantle Cell Lymphoma


Phase 2
18 Years
65 Years
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With Previously Untreated Mantle Cell Lymphoma


OBJECTIVES:

- To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed
mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin
hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine
(MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine
(R-bendamustine) and autologous stem cell transplant and to select a regimen for
further development.

- To assess the response rate and overall survival of patients with newly diagnosed MCL
treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT.

- To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine
and ASCT in patients with newly diagnosed MCL.

- To determine the prognostic value of quantitative minimal-residual disease (MRD)
monitoring in the peripheral blood of MCL patients after induction therapy and serially
after high-dose chemotherapy and ASCT on treatment outcome.

- To bank diagnostic tissue sections for future translational research studies.

OUTLINE: This is a multicenter study. Patients are stratified according to risk
classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk
vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms.

- Arm I (induction therapy):

- Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day
1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin
hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and
12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15.
Patients with responsive disease after course 1 proceed to course 2.

- Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22
hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and
leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection
after completion of course 2.

- Each course is 21 days long and continues in the absence of disease progression or
unacceptable toxicity.

- Arm II (induction therapy):

- Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride
IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in
the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks
later, patients with responsive disease receive 2 additional courses of treatment.

- Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV
and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell
collection about 26 days later.

Consolidation therapy: Patients receive one of the following preparative regimens.

- BCV* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4
hours on day -4; and cyclophosphamide IV over 1 hour on day -2.

- BEAM* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1
hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and
melphalan IV on day -1.

- TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice
daily on days -8 to -5. Patients also receive etoposide IV on day -4 and
cyclophosphamide IV over 1 hour on day -2.

- NOTE: * Patients 61 years of age or older receive either BCV or BEAM.

- NOTE: * *TBI may not be used for patients 61 years of age and older. Stem cell
transplantation: Patients then undergo autologous peripheral blood stem cell
transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 2 years, and then annually for up to 8 years from registration.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- All patients must have previously untreated stage III, IV, or bulky stage II mantle
cell lymphoma (MCL)

- A diagnosis of MCL must be confirmed by histopathological diagnosis including
immunohistochemistry and flow cytometry documenting both of the following
phenotypes:

- CD19+ or CD20+

- Cyclin D1+ or evidence of the t(11;14) translocation by cytogenetics or
FISH

- Adequate sections from the original diagnostic specimen must be available for
submission for central review

- An adequate biopsy requires sufficient tissue to establish the architecture and
a WHO histologic subtype with certainty

- Core biopsies, especially multiple core biopsies, MAY be adequate, but
needle aspirations or cytologies are not adequate

- Bone marrow core biopsy or clot sections (not aspirates) may be used as
diagnostic material if it is significantly involved and are the only diagnostic
material available

- All patients must have bidimensional measurable disease documented on the Lymphoma
Baseline Tumor Assessment Form (Form #48031)

- Patients who also have non-measurable disease in addition to measurable disease
must have all nonmeasurable disease assessed within 28 days prior to
registration

- Patients must not have clinical evidence of central nervous system (CNS) involvement
by lymphoma

- Any laboratory or radiographic tests performed prior to registration to assess
CNS involvement must be negative

- Patients must have a unilateral/bilateral bone marrow aspirate and biopsy for staging
performed within 42 days prior to registration

- If the biopsy cannot be performed but the aspirate is unequivocally consistent
with mantle cell lymphoma, this will be considered adequate for staging purposes

- Patients must be eligible for stem cell transplantation by institutional guidelines
with the plan that transplant will be conducted at a cooperative group-approved
transplant center

- Patients must be planning to undergo stem cell transplantation within 84 days
after day 1 of the last induction course

- Patients must have had at least 1.5 X 10^6 CD34^+ cells/kg collected and stored
prior to second registration for stem cell transplantation

PATIENT CHARACTERISTICS:

- Zubrod performance status of 0-2

- Bilirubin ≤ 3 times upper limit of normal (ULN)

- Serum creatinine ≤ 2.0 times ULN

- ALT and AST ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Platelet count ≥ 100,000/mcL, unless due to bone marrow infiltration by lymphoma

- All patients ≥ 45 years of age must have an echocardiogram (ECHO) or MUGA scan within
42 days prior to registration (whichever method is used at baseline must be used at
restaging)

- Patients < 45 years of age should have ECHO/MUGA only if clinically indicated

- Patients with an ejection fraction < institutional lower limit of normal (ILLN)
are not eligible

- Serum LDH and a CBC with differential must be measured within 28 days prior to
registration

- Patients known to be HIV positive, or who have a history of solid organ
transplantation, are ineligible

- No active hepatitis

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated
Stage I or II cancer from which the patient is currently in complete remission; or
any other cancer from which the patient has been disease-free for 5 years

- Pregnant or nursing women may not participate

- Women or men of reproductive potential may not participate unless they have agreed to
use an effective contraceptive method

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PFS at 2 years

Safety Issue:

No

Principal Investigator

Steven H. Bernstein, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

James P. Wilmot Cancer Center

Authority:

Unspecified

Study ID:

CDR0000707601

NCT ID:

NCT01412879

Start Date:

November 2011

Completion Date:

Related Keywords:

  • Lymphoma
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
CCOP - WichitaWichita, Kansas  67214-3882
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
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
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
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
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Methodist Medical Center of IllinoisPeoria, Illinois  61636
CCOP - DaytonKettering, Ohio  45429
CCOP - GreenvilleGreenville, South Carolina  29615
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
MultiCare Regional Cancer Center at Tacoma General HospitalTacoma, Washington  98405
CCOP - NorthwestTacoma, Washington  98405-0986
City of Hope Comprehensive Cancer CenterDuarte, California  91010
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Olympic Hematology and OncologyBremerton, Washington  98310
Skagit Valley Hospital Cancer Care CenterMt. Vernon, Washington  98273
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Harborview Medical CenterSeattle, Washington  98104
Group Health Central HospitalSeattle, Washington  98104
North Puget Oncology at United General HospitalSedro-Wooley, Washington  98284
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Hematology Oncology Associates - SkokieSkokie, Illinois  60076
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Hematology and Oncology AssociatesChicago, Illinois  60611
Eureka Community HospitalEureka, Illinois  61530
Mason District HospitalHavana, Illinois  62644
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Middletown Regional HospitalMiddletown, Ohio  45044
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Fulton County Health CenterWauseon, Ohio  43567
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Providence Milwaukie HospitalMilwaukie, Oregon  97222
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Minor and James Medical, PLLCSeattle, Washington  98104
Polyclinic First HillSeattle, Washington  98122
Southwest Washington Medical Center Cancer CenterVancouver, Washington  98668
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
St. Francis HospitalFederal Way, Washington  98003
St. Clare HospitalLakewood, Washington  98499-0998
Providence St. Peter Hospital Regional Cancer CenterOlympia, Washington  98506
Good Samaritan Cancer CenterPuyallup, Washington  98371
Allenmore HospitalTacoma, Washington  98411-0414
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
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
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
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
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
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Hematology Oncology CenterElyria, Ohio  44035
Community Cancer CenterElyria, Ohio  44035
Wayne HospitalGreenville, Ohio  45331
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
St. Joseph Cancer CenterBellingham, Washington  98225
Providence Centralia HospitalCentralia, Washington  98531-9027
Columbia Basin HematologyKennewick, Washington  99336
Harrison Poulsbo Hematology and OnocologyPoulsbo, Washington  98370
Evergreen Hematology and Oncology, PSSpokane, Washington  99218
Franciscan Cancer Center at St. Joseph Medical CenterTacoma, Washington  98405-3004
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Saint Louis University Cancer CenterSaint Louis, Missouri  63110
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
Cancer Centers of the Carolinas - Grove CommonsGreenville, South Carolina  29605
Cancer Centers of the Carolinas - Faris RoadGreenville, South Carolina  29605
Cancer Centers of the Carolinas - Greer Medical OncologyGreer, South Carolina  29650
Cancer Centers of the Carolinas - SenecaSeneca, South Carolina  29672
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Galesburg Clinic, PCGalesburg, Illinois  61401
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - GalesburgGalesburg, Illinois  61401
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
Provena St. Mary's Regional Cancer Center - KankakeeKankakee, Illinois  60901
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
Baylor University Medical Center - DallasDallas, Texas  75246
Northwest Cancer Specialists at Vancouver Cancer CenterVancouver, Washington  98684
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
Providence Newberg Medical CenterNewberg, Oregon  97132
Willamette Falls HospitalOregon City, Oregon  97045
Island Hospital Cancer Care Center at Island HospitalAnacortes, Washington  98221
Highline Medical Center Cancer CenterBurien, Washington  98166
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
Overlake Cancer Center at Overlake Hospital Medical CenterBellevue, Washington  98004
Providence Regional Cancer PartnershipEverett, Washington  98201
Cancer Center of Kansas, PA - McPhersonMcPherson, Kansas  67460
St. Joseph Regional Medical CenterLewiston, Idaho  83501
Swedish Medical Center - Issaquah CampusIssaquah, Washington  98029