Clinical trial NCT00301938 (phase 1, status: completed)
Conditions: accelerated phase chronic myelogenous leukemia, adult acute megakaryoblastic leukemia (m7), adult acute minimally differentiated myeloid leukemia (m0), adult acute monoblastic leukemia (m5a), adult acute monocytic leukemia (m5b), adult acute myeloblastic leukemia with maturation (m2), adult acute myeloblastic leukemia without maturation (m1), adult acute myeloid leukemia with 11q23 (mll) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (m4), adult acute promyelocytic leukemia (m3), adult erythroleukemia (m6a), adult pure erythroid leukemia (m6b), blastic phase chronic myelogenous leukemia, myelodysplastic/myeloproliferative neoplasms, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, t-cell adult acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, untreated adult acute myeloid leukemia
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C94.21, C94.22, C94.20, C7A.1, C93.01, C93.02, C93.00, C93.Z1, C93.Z2, C93.91, C93.92, C93.01, C93.02, C93.Z0, C92.01, C92.02, C92.00, C92.01, C92.02, C92.00, R19.5, H35.09, M26.50, M26.59, Q99.8, R06.89, R06.9, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C92.51, C92.52, C93.11, C93.12, C93.31, C93.32, C92.50, C94.01, C94.02, C94.00, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, D46.Z, D46.9, C94.6, D46.C, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, M94.1, A68.9, A68.0, A68.1, M35.6, D75.1, E26.1, N91.1, N91.4, N94.5, A51.41, A51.43, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: 7-hydroxystaurosporine, perifosine
SMILES: [H][C@]1(O)N=C(O)C2=C3C4=CC=CC=C4N4C3=C3N(C5=CC=CC=C5C3=C12)[C@@]1(C)O[C@]4([H])C[C@@]([H])(NC)[C@@]1([H])OC, CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed hematologic malignancy of 1 of the following
             types:

               -  Relapsed or refractory acute myelogenous leukemia (AML)

                    -  Patients with acute promyelocytic leukemia t(15;17) are eligible provided
                       they failed a prior tretinoin and arsenic-containing regimen

                         -  Patients should be either refractory to both agents (absence of durable
                            hematologic response) OR relapsed after a complete response duration of
                            < 6 months

               -  Relapsed or refractory pre-B-cell or T-cell acute lymphoblastic leukemia (ALL)

               -  Chronic myelogenous leukemia (CML) in accelerated or blastic phase that is
                  refractory to imatinib mesylate

                    -  Must have evidence of disease progression despite continued treatment with
                       imatinib mesylate

               -  AML arising in the setting of underlying myelodysplastic syndromes (MDS) and/or
                  myeloproliferative disorders (MPD)

               -  Secondary or therapy-related AML

               -  De novo AML or pre-B-cell or T-cell ALL in adults > 60 years of age with
                  poor-risk features, such as complex (≥ 3) or adverse cytogenetics

                    -  The following are considered adverse cytogenetic abnormalities for AML:

                         -  -5q

                         -  7q-

                         -  9q-

                         -  20q-

                         -  abn12p

                         -  +21

                         -  +8

                         -  t(6;9)

                         -  t(6;11)

                         -  t(11;19)

                         -  -7

                         -  -5

                         -  inv3/t(3;3)

                         -  abn11q23

                         -  abn17p

                         -  abn21q

                         -  t(9;22) refractory to imatinib mesylate

                    -  The following are considered adverse cytogenetic abnormalities for ALL:

                         -  t(9;22) refractory to imatinib mesylate

                         -  Hypodiploidy

                         -  t(4;11)

                         -  t(1;19)

               -  Myelodysplastic Syndromes (MDS) meeting 1 of the following criteria:

                    -  Intermediate and high risk (i.e., International Prognostic Scoring System
                       [IPSS] ≥ 1.5) MDS that is refractory or has progressed after treatment with
                       azacitidine and/or decitabine

                    -  Intermediate and high risk (i.e., IPSS ≥ 1.5) MDS with a 5q- cytogenetic
                       abnormality that is refractory or has progressed after treatment with
                       lenalidomide, azacitidine, or decitabine

                    -  Intermediate 2 and high risk MDS without 5q- cytogenetic abnormality that is
                       refractory or has progressed after azacitidine or decitabine

                         -  Original 5q must also be refractory to lenalidomide

          -  Received OR ineligible for established curative regimens, including stem cell
             transplantation

          -  No active CNS leukemia

          -  ECOG performance status (PS) 0-2 OR Karnofsky PS ≥ 60%

          -  Total or direct bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  AST/ALT ≤ 2.5 times ULN

          -  Creatinine ≤ 2 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study treatment

          -  No hyperleukocytosis (i.e., WBC > 30,000/mm^3) (recent treatment with hydroxyurea to
             prevent impending leukostasis allowed provided there has been no dose increase for ≥ 1
             week)

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to UCN-01 or perifosine

          -  No intrinsic impaired organ function

          -  No active, uncontrolled infection

               -  Infection that is controlled with antibiotics allowed

          -  No symptomatic cardiac disease

          -  No active ischemia on EKG

          -  LVEF ≥ 40% by echocardiogram or MUGA

               -  Patients with a history of cardiac disease or mediastinal radiation should
                  undergo testing of ventricular function

          -  No poorly controlled diabetes mellitus

          -  No psychiatric illness or social situation that would preclude giving informed consent
             or complying with study requirements

          -  No HIV positivity

          -  See Disease Characteristics

          -  At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for carmustine or
             mitomycin C) and recovered

          -  At least 4 weeks since prior radiotherapy and recovered

          -  At least 4 weeks since prior autologous stem cell transplantation (SCT)

          -  At least 90 days since prior allogeneic SCT

               -  No evidence of graft vs host disease

          -  At least 2 weeks since prior immunosuppressive therapy

          -  No concurrent hematopoietic growth factors or biologic agents

          -  No other concurrent investigational agents, chemotherapy, radiotherapy, or
             immunotherapy

          -  No other concurrent anticancer therapy