Status:

COMPLETED

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

Lead Sponsor:

National Cancer Institute (NCI)

Conditions:

Accelerated Phase Chronic Myelogenous Leukemia

Adult Acute Megakaryoblastic Leukemia (M7)

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief 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 mye...

Detailed Description

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 l...

Eligibility Criteria

Inclusion

  • 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

Exclusion

    Key Trial Info

    Start Date :

    December 1 2005

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    Estimated Enrollment :

    30 Patients enrolled

    Trial Details

    Trial ID

    NCT00301938

    Start Date

    December 1 2005

    Last Update

    September 30 2013

    Active Locations (1)

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    Page 1 of 1 (1 locations)

    1

    University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, United States, 21201-1595