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

Phase 1

Terminated

• Conditions: 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
• Interventions: Drug: SJG-136

• Registration Number: NCT00301769
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

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

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.

Study Timeline

• Study Start: 2005-12
• Study First Submitted: 2006-03-09
• Study First Submitted QC: 2006-03-09
• Study First Posted: 2006-03-13
• Primary Completion: 2009-02
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-27
• Last Update Posted: 2013-09-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	SJG-136	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.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States