7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

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