SJG-136 in Treating Patients With Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndromes, Blastic Phase Chronic Myelogenous Leukemia, or Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of SJG-136 in treating patients with relapsed or refractory acute leukemia, myelodysplastic syndromes, blastic phase chronic myelogenous leukemia, or chronic lymphocytic leukemia. Drugs used in chemotherapy, such as SJG-136, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Detailed Description
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OBJECTIVES: I. Establish the maximum tolerated dose of SJG-136 in patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) myelodysplastic syndrome (MDS), chronic myelogenous leukemia in blastic phase (CML-BP), or chronic lymphocytic leukemia (CLL). II. Determine dose-limiting toxicities and pharmacokinetics of this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive SJG-136 IV over 15 minutes on days 1-5. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of SJG-136 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.

Official Title
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A Phase I Study of SJG-136 in Patients With Advanced Leukemia

Conditions
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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), Blastic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Chronic Lymphocytic Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: SJG-136


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia Acute lymphoblastic leukemia Myelodysplastic syndromes Chronic myelogenous leukemia in blastic phase Chronic lymphocytic leukemia Relapsed or refractory disease No immediately available, potentially curable options (e.g., stem cell transplantation) available Bilirubin normal (unless elevated due to Gilbert's syndrome) HIV positivity allowed provided CD4 counts are normal with no AIDS-defining disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situations that would limit study compliance Recovered from prior therapy ECOG performance status =< 2 SGOT and SGPT =< 2.5 times upper limit of normal (ULN) Creatinine normal OR creatinine clearance >= 60 mL/min Primary resistance (i.e., failed to achieve a complete remission [CR] to a standard induction regimen) or relapsed after achievement of a CR. Must have documented failure to last cytotoxic regimen prior to study entry. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: No known CNS disease No history of allergic reactions attributed to compounds of similar chemical or biologic composition to SJG-136 More than 7 days since radiotherapy No concurrent combination antiretroviral therapy for HIV-positive patients No other anti-leukemia agents except hydroxyurea =< 5 grams/day =< 14 days prior to and during first course of treatment to control blood counts

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive SJG-136 IV over 15 minutes on days 1-5. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of SJG-136 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD. | Drug: SJG-136<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) |  | 21 days |