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A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts


Phase 3
60 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

Thank you

Trial Information

A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts


OBJECTIVES:

- Compare the overall survival and progression-free survival of elderly patients with
newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in
transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or
without zosuquidar trihydrochloride.

- Compare the complete remission rate of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the systemic exposure of daunorubicin and cytarabine in patients treated with
zosuquidar trihydrochloride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to age (60-69 years vs 70 years and over), disease (refractory
anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]),
and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

- Induction:

- Arm I: Patients receive daunorubicin via intravenous (IV) infusion over 10-15
minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also
receive cytarabine IV continuously on days 1-7.

- Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also
receive placebo IV over 6 hours on days 1-3.

Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim
(GM-CSF) subcutaneously (SC) or IV daily until blood counts recover. Patients who have
evidence of persistent AML are eligible to receive a second identical course of induction
chemotherapy.

- Consolidation I (beginning within 8 weeks after documentation of complete remission
[CR] or measurable remission [MR]): Patients who achieve a CR or MR receive cytarabine
IV over 1 hour once or twice daily on days 1-6 and GM-CSF or G-CSF SC or IV beginning
on day 7 and continuing until blood counts recover.

- Consolidation II: Patients who have maintained peripheral blood evidence of a remission
receive daunorubicin, cytarabine, and zosuquidar trihydrochloride or placebo as in
induction chemotherapy. Patients also receive GM-CSF or G-CSF SC or IV beginning on day
8 or after last cytarabine dose and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1
year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 450 patients (225 per treatment arm) accrued over 4.1
years.


Inclusion Criteria:



One of the following disorders:

- Acute myeloid leukemia (AML), defined as >30% myeloblasts on the marrow aspirate or
peripheral blood differential and any French-American-British (FAB) subtype except M3
(i.e., acute promyelocytic leukemia)

- Refractory anemia with excess blasts (RAEB), defined as 11-20% myeloblasts on bone
marrow aspirate or peripheral blood differential, provided there are other criteria
for high-risk disease

- Refractory anemia with excess blasts in transformation (RAEB-T), defined as 21-30%
myeloblasts on bone marrow aspirate or peripheral blood differential

- Participants may have secondary AML

- Age greater than 60 years

- ECOG performance status of 0 to 3

- Total serum bilirubin < 3 mg/dL

- Serum creatinine < 2 mg/dL

- Cardiac ejection fraction of > 45%

Exclusion Criteria:

- Blastic transformation of chronic myelogenous leukemia

- CNS leukemia

- Prior chemotherapy for AML, with the exception of hydroxyurea

- For women: pregnant or breast feeding

- Other malignancy for which participant is currently receiving treatment

- Concurrent treatment with other colony-stimulating factors

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Overall Survival (OS)

Outcome Description:

Time from randomization to death. Patients alive at last follow-up were censored.

Outcome Time Frame:

Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter

Safety Issue:

No

Principal Investigator

Larry D. Cripe, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Indiana University Melvin and Bren Simon Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000257122

NCT ID:

NCT00046930

Start Date:

July 2002

Completion Date:

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • adult acute monocytic leukemia (M5b)
  • adult acute erythroid leukemia (M6)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • secondary acute myeloid leukemia
  • untreated adult acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Anemia, Aplastic

Name

Location

Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
CCOP - WichitaWichita, Kansas  67214-3882
CCOP - Southern Nevada Cancer Research FoundationLas Vegas, Nevada  89106
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
CCOP - Northern New JerseyHackensack, New Jersey  07601
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
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
North Suburban Medical CenterThornton, Colorado  80229
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Methodist Cancer Center at Methodist HospitalIndianapolis, Indiana  46202
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Baystate Regional Cancer Program at D'Amour Center for Cancer CareSpringfield, Massachusetts  01199
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
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
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical CenterLa Crosse, Wisconsin  54601
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Rush University Medical CenterChicago, Illinois  60612-3824
MetroHealth's Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44106
Wesley Medical CenterWichita, Kansas  67214
CCOP - Colorado Cancer Research Program, IncorporatedDenver, Colorado  80224
Hillman Cancer Center at University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15236
Tufts - New England Medical CenterBoston, Massachusetts  02111
Evanston Northwestern Health Care - Evanston HospitalEvanston, Illinois  60201
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve UniversityCleveland, Ohio  44106
Sioux Valley Hospital and University of South Dakota Medical CenterSioux Falls, South Dakota  57117-5134
St. Luke's Hospital Cancer CenterBethlehem, Pennsylvania  18015
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
Aultman Hospital Cancer Center at Aultman Health FoundationCanton, Ohio  44710-1799
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Siouxland Hematology-Oncology AssociatesSioux City, Iowa  51101
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - KingmanKingman, Kansas  67068
Southwest Medical CenterLiberal, Kansas  67901
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Pratt Cancer Center of KansasPratt, Kansas  67124
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, P.A.Wichita, Kansas  67208
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas, P.A. - WichitaWichita, Kansas  67214
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
MBCCOP-Medical College of Georgia Cancer CenterAugusta, Georgia  30912-4000
Leo W. Jenkins Cancer Center at Pitt County Memorial HospitalGreenville, North Carolina  27858-4354
University of Virginia Cancer CenterCharlottesville, Virginia  22908
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
University Medical Center of Southern NevadaLas Vegas, Nevada  89102
St. Mary-Corwin Regional Medical CenterPueblo, Colorado  81004
Hematology and Oncology AssociatesChicago, Illinois  60611
St. Joseph Mercy Cancer Center at St. Joseph Mercy HospitalAnn Arbor, Michigan  48106-0995
Virginia Piper Cancer Institute at Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Medical CenterRobbinsdale, Minnesota  55422-2900
Booker Cancer Center at Riverview Medical CenterRed Bank, New Jersey  07701
Hematology and Oncology AssociatesScranton, Pennsylvania  18510
Park Nicollet ClinicSt. Louis Park, Minnesota  55416
McFarland Clinic, P.C.Ames, Iowa  50010
Geisinger Medical GroupState College, Pennsylvania  16801
Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
CCOP - Mayo Clinic Scottsdale Oncology ProgramScottsdale, Arizona  85259
H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612
Guthrie Medical Center - SayreSayre, Pennsylvania  18840
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Watson Clinic, LLCLakeland, Florida  33804-5000