This phase I trial is studying the side effects and best dose of 7-hydroxystaurosporine when given together with perifosine in treating patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. 7-Hydroxystaurosporine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as perifosine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving 7-hydroxystaurosporine together with perifosine may kill more cancer cells.

PRIMARY OBJECTIVES:

I. Define the maximum tolerated dose and recommended phase II dose of UCN-01 (7-hydroxystaurosporine) administered after perifosine in patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or high risk myelodysplastic disorders.

SECONDARY OBJECTIVES:

I. Evaluate the safety and toxicity of UCN-01 administered after perifosine in these patients.

II. Evaluate the safety and toxicity of perifosine administered after UCN-01 in these patients.

III. Document responses in patients treated with this regimen. IV. Observe the pharmacokinetics of both perifosine and UCN-01 when administered in combination.

V. Study the pharmacodynamics of perifosine alone, UCN-01 alone, and in combination in leukemic blast cells.

OUTLINE: This is a multicenter, dose-escalation study of 7-hydroxystaurosporine. The first patients enrolled in the study are assigned to arm 1. Once the maximum tolerated dose (MTD) is determined in arm 1, subsequent patients are enrolled in arm 2.

ARM 1: Patients receive a loading dose of oral perifosine every 6 hours on day 1 followed by a maintenance dose once daily on days 2-28 of course 1 and then once daily on days 1-28 in all subsequent courses. Patients also receive 7-hydroxystaurosporine intravenously (IV) over 3 hours on day 4. Cohorts of 3-6 patients receive escalating doses of 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

ARM 2: Patients receive 7-hydroxystaurosporine IV over 3 hours on day 1 at the MTD determined in group I. Patients also receive oral perifosine as a loading dose every 6 hours on day 4 followed by a maintenance dose once daily on days 5-28 of course 1 and then once daily on days 1-28 in all subsequent courses. In both groups, treatment repeats every 28 days for ≥ 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete remission (CR) or a CR with incomplete hematologic recovery receive 4 additional courses beyond documentation of CR. Patients who achieve a partial remission or hematologic improvement may continue treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days and then periodically thereafter.

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