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S0521, A Randomized Trial of Maintenance Versus Observation for Patients With Previously Untreated Low and Intermediate Risk Acute Promyelocytic Leukemia (APL), Phase III


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

S0521, A Randomized Trial of Maintenance Versus Observation for Patients With Previously Untreated Low and Intermediate Risk Acute Promyelocytic Leukemia (APL), Phase III


OBJECTIVES:

- Compare disease-free survival in patients with previously untreated low- or
intermediate-risk acute promyelocytic leukemia treated with induction and consolidation
combination chemotherapy with or without gemtuzumab ozogamicin followed by maintenance
therapy comprising tretinoin, mercaptopurine, and methotrexate vs
observation.(Randomization and observation arm closed as of 05/27/10)

- Assess the toxicity of these regimens in these patients.

- Determine whether gene expression profiling assessed prior to treatment is predictive
of resistance to remission induction chemotherapy and correlate with detectable minimal
residual disease post-consolidation therapy.

- Determine the relapse-free survival of patients who respond to induction chemotherapy.

- Assess, preliminarily, the outcomes of patients who fail to achieve or maintain
PCR-negative PML-RARα fusion gene after consolidation therapy when treated with
gemtuzumab ozogamicin.

OUTLINE: This is a randomized, multicenter study.

- Induction therapy: Patients receive oral tretinoin twice daily until morphologic
complete remission (CR) or for a maximum of 90 days in the absence of disease
progression or unacceptable toxicity. Patients also receive cytarabine IV continuously
on days 3-9 and daunorubicin hydrochloride IV on days 3-6.

- Consolidation therapy: Patients who achieve CR, CR with incomplete blood count recovery
(CRi), or partial remission (PR) after induction therapy receive arsenic trioxide IV
over 2 hours 5 days a week for 5 weeks. After a 2-week rest period, patients receive a
second course of arsenic trioxide. Within 14-30 days after blood count recovery,
patients receive oral tretinoin twice daily on days 1-7 and daunorubicin hydrochloride
IV on days 1-3. Patients receive a second course of tretinoin and daunorubicin
hydrochloride after adequate blood count recovery.

- Post-consolidation therapy: Patients who do not achieve molecular CR (CRm), but do
achieve CR or CRi and are still PML-RARα-positive after consolidation therapy, receive
gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment repeats every 14 days
for up to 6 courses or until PML-RARα-negative by PCR. (closed as of 05/27/10)Patients
are stratified according to age (18 to 60 years vs > 60 years), acute promyelocytic
leukemia (APL) risk group (low vs intermediate), and if the patient received
consolidation therapy courses 3 or 4 (yes vs no) regardless of their CRm response.
These patients are randomized to 1 of 2 treatment arms. (Randomization and observation
arm closed as of 05/27/10) All patients are non-randomly assigned to receive
post-consolidation therapy.

- Arm I: Beginning 14-30 days after blood count recovery, patients receive oral
tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14,
and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year.

- Arm II: Patients receive no further chemotherapy. Patients are followed every 3
months for 1 year. (Randomization and observation arm closed as of 05/27/10)
Patients undergo blood collection periodically for cytogenetic studies. Samples
are analyzed for PML-RARα fusion gene via reverse transcriptase-polymerase chain
reaction (RT-PCR) assay and gene expression profiling.

After completion of study treatment, patients are followed every 3 months for 1 year, every
6 months for 1 year, and then annually for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Cytologically confirmed acute promyelocytic leukemia (APL) or the variant form of APL

- Previously untreated disease

- Low- or intermediate-risk disease

- Low-risk disease, defined as WBC ≤ 10,000/mm^3 and platelet count >
40,000/mm^3

- Intermediate-risk disease, defined as WBC ≤ 10,000/mm^3 and platelet count
≤ 40,000/mm^3

- WBC and platelet count confirming low- or intermediate-risk disease must be
obtained within 48 hours prior to study registration unless the patient
received tretinoin therapy prior to study registration in which case the
WBC and platelet count must be obtained within 48 hours prior to study
therapy

- PML-RARα fusion gene positive by reverse transcriptase-polymerase chain reaction
(RT-PCR) assay

- No recurrent disease

- Must be registered on clinical trials SWOG-9007 and SWOG-S9910

- Specimens must be collected prior to tretinoin therapy and may be collected
after tretinoin therapy

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-3

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception for ≥ 1 month prior to, during, and
for 2 months after completion of study treatment

- No unstable cardiac arrhythmia or unstable angina

- No other malignancy within the past 5 years except for the following:

- Adequately treated basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Adequately treated stage I or II cancer (except for highly aggressive
malignancies with a high rate of early relapse) currently in complete remission

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 1 prior dose of intrathecal chemotherapy for acute leukemia

- No prior systemic chemotherapy, hydroxyurea, or leukapheresis for acute leukemia

- Prior tretinoin at a dose of ≤ 45 mg/m^2/day allowed provided it was received ≤
5 days prior to study registration

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Steven E. Coutre, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Stanford University

Authority:

United States: Federal Government

Study ID:

CDR0000553210

NCT ID:

NCT00492856

Start Date:

June 2007

Completion Date:

Related Keywords:

  • Leukemia
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute promyelocytic leukemia (M3)
  • untreated adult acute myeloid leukemia
  • Leukemia
  • Leukemia, Promyelocytic, Acute

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - North Shore University HospitalManhasset, New York  11030
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
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
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
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
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
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
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
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
St. Rita's Medical CenterLima, Ohio  45801
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
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
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Avera Cancer InstituteSioux Falls, South Dakota  57105
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Froedtert Hospital and Medical College of WisconsinMilwaukee, Wisconsin  53226-3596
Methodist Medical Center of IllinoisPeoria, Illinois  61636
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Sutter Cancer CenterSacramento, California  95816
Wesley Medical CenterWichita, Kansas  67214
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Our Lady of Mercy Medical Center Comprehensive Cancer CenterBronx, New York  10466
CCOP - Hematology-Oncology Associates of Central New YorkEast Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Community Medical CenterMissoula, Montana  59801
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
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
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
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
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
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
Sutter Cancer Center at Roseville Medical CenterRoseville, California  95661
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Hematology and Oncology AssociatesChicago, Illinois  60611
Eureka Community HospitalEureka, Illinois  61530
Mason District HospitalHavana, Illinois  62644
Midwest Center for Hematology/OncologyJoliet, Illinois  60432
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
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
Fort Wayne Medical Oncology and HematologyFort Wayne, Indiana  46815
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Minor and James Medical, PLLCSeattle, Washington  98104
Polyclinic First HillSeattle, Washington  98122
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Stanford Cancer CenterStanford, California  94305-5824
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Hematology Oncology Associates of Illinois - BerwynBerwyn, Illinois  60402
Kellogg Cancer Care CenterHighland Park, Illinois  60035
La Grange Oncology Associates - GenevaNaperville, Illinois  60563
Cancer Care and Hematology Specialists of Chicagoland - NilesNiles, Illinois  60714
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
Tammy Walker Cancer Center at Salina Regional Health CenterSalina, Kansas  67401
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
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
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
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Monter Cancer Center of the North Shore-LIJ Health SystemLake Success, New York  11042
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Barberton Citizens HospitalBarberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
St. Joseph Cancer CenterBellingham, Washington  98225
Columbia Basin HematologyKennewick, Washington  99336
Harrison Poulsbo Hematology and OnocologyPoulsbo, Washington  98370
Evergreen Hematology and Oncology, PSSpokane, Washington  99218
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Rocky Mountain OncologyCasper, Wyoming  82609
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Saint Louis University Cancer CenterSaint Louis, Missouri  63110
Kinston Medical SpecialistsKinston, North Carolina  28501
Great Falls, Montana  59405
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Galesburg Clinic, PCGalesburg, Illinois  61401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
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