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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: 7-hydroxystaurosporine; Enzyme Inhibitors; Staurosporine

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