Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts
Intervention: filgrastim; sargramostim; cytarabine; daunorubicin hydrochloride; zosuquidar trihydrochloride; Placebo
Intervention description: 250 μg/m2/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; 5 μg/kg/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; 100 mg/m²/day by continuous intravenous infusion for 7 days (days 1-7).; 45 mg/m²/day by 10 - 15 minute intravenous infusion for 3 days (days 1, 2, and 3).; Zosuquidar 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3.
The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3.; Placebo 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3.
The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3. Placebo consisted of a 1:1000 dilution of Infuvite, appropriately colored.
Intervention MeSH terms: Cytarabine; Daunorubicin; Molgramostim; Lenograstim; Sargramostim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 449.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: 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)

Summary:

      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Zosuquidar trihydrochloride, a modulator of multidrug resistance
      (MDR), may help daunorubicin and cytarabine kill more cancer cells by making cancer cells
      more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more
      effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or
      anemia.

      PURPOSE: This randomized phase III trial is studying how well giving zosuquidar
      trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and
      cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or
      anemia that has not responded to previous treatment.
    

Eligibility criteria:

        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