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Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT00801489

Description:

This phase II trial studies the side effects and how well fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride work in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as fludarabine phosphate, cytarabine, and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Immunotherapy with monoclonal antibodies, such as gemtuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Colony-stimulating factors, such as filgrastim-sndz, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride may kill more cancer cells.

Related Conditions:
  • Acute Myeloid Leukemia
  • Refractory Anemia with Excess Blasts
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
  • Official Title: A Phase 2 Study of Fludarabine, Cytarabine, Filgrastim-sndz,Gemtuzumab Ozogamicin and Idarubicin in Newly Diagnosed Core Binding Factor Associated Acute Myelogenous Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2007-0147
  • SECONDARY ID: NCI-2012-01659
  • SECONDARY ID: 2007-0147
  • NCT ID: NCT00801489

Conditions

  • Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
  • Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
  • Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1
  • de Novo Myelodysplastic Syndrome
  • High Risk Myelodysplastic Syndrome
  • Inv(16)
  • Myelodysplastic Syndrome With Excess Blasts
  • t(16;16)
  • t(8;21)
  • Untreated Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Treatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)
Decitabine5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineTreatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)
Filgrastim-sndzFilgrastim Biosimilar Filgrastim-sndz, ZarxioTreatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)
Gemtuzumab OzogamicinCalicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676Treatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)
Idarubicin4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDRTreatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)

Purpose

This phase II trial studies the side effects and how well fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride work in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as fludarabine phosphate, cytarabine, and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Immunotherapy with monoclonal antibodies, such as gemtuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Colony-stimulating factors, such as filgrastim-sndz, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving fludarabine phosphate, cytarabine, filgrastim-sndz, gemtuzumab ozogamicin, and idarubicin hydrochloride may kill more cancer cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the safety of a regimen incorporating fludarabine phosphate (fludarabine),
      high-dose cytarabine, filgrastim-sndz, gemtuzumab ozogamicin and idarubicin hydrochloride
      (idarubicin) in patients with untreated inv(16) or t(8;21) acute myeloid leukemia (AML).

      II. Evaluate the complete remission rates achieved in this population with this regimen.

      SECONDARY OBJECTIVES:

      I. Assess the proportion of patients with untreated inv(16) or t(8;21) AML who, having
      entered complete remission (CR) on this regimen, remain alive in CR two years from CR date.

      II. Assess whether the quantitative polymerase chain reaction (Q-PCR) results can be used in
      detecting relapse in these patients.

      OUTLINE:

      REMISSION INDUCTION: Patients receive filgrastim-sndz subcutaneously (SC) once daily (QD)
      beginning on day -1 and continuing until blood count recovery. Patients also receive
      fludarabine phosphate intravenously (IV) over 30 minutes on days 1-5, cytarabine IV over 4
      hours on days 1-5, gemtuzumab ozogamicin IV over 2 hours on day 1, and idarubicin
      hydrochloride IV over 30 minutes on days 3 and 4. Patients not in remission after their first
      induction therapy may repeat remission induction therapy.

      POST-REMISSION THERAPY: Patients receive filgrastim-sndz SC on day -1, fludarabine phosphate
      IV over 30 minutes on days 1-3, cytarabine IV over 4 hours on days 1-3, gemtuzumab ozogamicin
      IV over 2 hours on day 1 of courses 1 or 2 and 5 or 6, and idarubicin hydrochloride IV over
      30 minutes on days 2 and 3 (day 2 only of courses 3-6). Treatment repeats every 4-6 weeks for
      up to 6 courses in the absence of disease progression or unacceptable toxicity.

      FURTHER MODIFICATION OF POST-REMISSION THERAPY: Patients older than 60, with significant
      comorbidities, experiencing life-threatening complications, prolonged cytopenias, or not
      achieving complete molecular response may receive decitabine IV daily for 5 days after
      discussion with the principal investigator. Treatment repeats every 4-6 weeks for up to 12
      courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (filgrastim, fludara, cytara, gemtuzu, idarubicin)ExperimentalSee Detailed Description
  • Cytarabine
  • Decitabine
  • Filgrastim-sndz
  • Fludarabine Phosphate
  • Gemtuzumab Ozogamicin
  • Idarubicin

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have untreated AML, or high-risk myelodysplastic syndromes (MDS)
             (refractory anemia with excess blasts, [RAEB], or RAEB "in transformation" [RAEB-t])
             characterized by t(8;21), inv(16), or t(16;16); the presence of additional
             abnormalities is irrelevant

          -  Patients must provide written consent

          -  Participants will not be excluded based on performance status; for patients with
             Eastern Cooperative Oncology Group (ECOG) performance status >= to 3 the dosing
             schedule will be discussed with study chairman

          -  Patients with organ dysfunction will not be excluded from the study; for patients with
             evidence of organ dysfunction (creatinine >= 1.5, cardiac ejection fraction =< 50%,
             total bilirubin >=2 and aspartate aminotransferase [AST]/alanine aminotransferase
             [ALT] >= 3 times upper limit of normal [ULN]), dose adjustments/omissions will be made

          -  Up to one cycle of prior induction therapy will be permitted to include patients in
             whom presence of "good-risk" cytogenetics was initially missed; if the patient is in
             remission from induction therapy, he/she will receive post-remission therapy; if the
             patient is not in remission then he/she will receive induction therapy

          -  Patients of child bearing potential should practice effective methods of contraception

        Exclusion Criteria:

          -  Pregnant and lactating females will be excluded
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission rate
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

April 1, 2021