Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Condition: Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia-2; High Risk Myelodysplastic Syndrome; Myeloproliferative Neoplasm
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and best dose of pomalidomide after combination
      chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or high-risk
      myelodysplastic syndrome. Drugs used in chemotherapy, such as cytarabine, daunorubicin
      hydrochloride, and etoposide, work in different ways to stop the growth of cancer cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Pomalidomide may kill cancer cells by stopping blood flow to the cancer and by
      stimulating white blood cells to kill cancer cells. Giving more than one drug (combination
      chemotherapy) and pomalidomide may kill more cancer cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To define the maximum tolerated dose (MTD) of pomalidomide when given at the time of early
      lymphocyte recovery following intensive induction timed sequential therapy (TST) with
      cytarabine (cytosine arabinoside), daunorubicin hydrochloride (daunorubicin) and etoposide
      (AcDVP-16) in patients with newly diagnosed intermediate- and poor-risk acute myeloid
      leukemia and high-risk myelodysplastic syndrome (MDS).

      II. To evaluate the safety, tolerability and toxicity of pomalidomide given at the time of
      early lymphocyte recovery following induction AcDVP-16 chemotherapy in adults with newly
      diagnosed intermediate- and poor-risk acute myeloid leukemia and high-risk MDS.

      SECONDARY OBJECTIVES:

      I. To evaluate the safety, tolerability and toxicity of pomalidomide given as a continuation
      therapy following induction and/or consolidation chemotherapy in adults with newly diagnosed
      intermediate- and poor-risk acute myeloid leukemia and high-risk MDS.

      II. To document responses (complete remission [CR], CR with incomplete count recovery [CRi],
      partial remission [PR]) to AcDVP-16 followed by pomalidomide at the time of lymphocyte
      recovery in newly diagnosed adults with intermediate- and poor-risk acute myeloid leukemia
      (AML) and high-risk MDS, including duration of response, disease-free and overall survival.

      III. Correlative pharmacodynamics studies: a) to characterize the effects of pomalidomide on
      the functional dynamics of different lymphocyte subpopulations (effector T [Teff], regulatory
      T [Treg], natural killer [NK] cells) and its impact on tumor-associated antigen
      (TAA)-specific T cell immunity when given following induction and as a maintenance; b) to
      examine for the presence of minimal residual disease (MRD) before and after pomalidomide
      administration during induction and continuation therapy; c) to examine cereblon expression
      in primary leukemia cells at diagnosis and in sorted T cells prior to and after pomalidomide
      treatment.

      OUTLINE: This is a dose-escalation study of pomalidomide.

      INDUCTION: Patients receive cytarabine intravenously (IV) continuously and daunorubicin
      hydrochloride IV on days 1-3 (patients may otherwise receive idarubicin hydrochloride IV over
      10-15 minutes on days 1-3 if daunorubicin hydrochloride is unavailable), and etoposide IV
      over 3 hours on days 8-10. At the time of early lymphocyte recovery (after day +14), patients
      also receive pomalidomide orally (PO) for 10-21 days.

      CONSOLIDATION: Patients achieving CR or CRi receive cytarabine based treatment at the
      discretion of the treating investigator, with possible regimens comprising cytarabine IV
      continuously on days 1-3, and 10-12 and daunorubicin hydrochloride IV on days 1-3, or high-
      or medium-dose cytarabine IV every 12 hours on days 1, 3, and 5 for 1-4 courses.

      CONTINUATION: Patients achieving CR or CRi who did not undergo allogeneic stem cell
      transplant receive pomalidomide PO daily on days 1-21 beginning 6 weeks following blood count
      recovery. Treatment repeats every 4-6 weeks for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 2 years.
    

Intervention name(s): Cytarabine; Daunorubicin Hydrochloride; Etoposide; Idarubicin Hydrochloride; Laboratory Biomarker Analysis; Pharmacological Study; Pomalidomide
Intervention type(s): Drug; Drug; Drug; Drug; Other; Other; Drug
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Correlative studies; Correlative studies; Given PO
Other intervention name(s): .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-28453; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Idamycin; Idamycin PFS; Idarubicin HCl; IMI-30; SC-33428; Zavedos; 4-Aminothalidomide; Actimid; CC-4047; Imnovid; Pomalyst
Intervention MeSH terms: Cytarabine; Etoposide; Podophyllotoxin; Daunorubicin; Idarubicin; Etoposide phosphate; Pomalidomide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment