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A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy

Phase 1
18 Years
Not Enrolling
Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy



- Determine the recommended phase II dose of AT7519M in patients with advanced or
metastatic solid tumors or refractory non-Hodgkin's lymphoma.

- Determine the safety, tolerability, toxicity profile, and dose-limiting toxicities of
this drug in these patients.

- Determine the pharmacokinetic profile of this drug in these patients.

- Correlate the toxicity profile with pharmacokinetics of this drug in these patients.


- Assess, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive AT7519M IV over 1-3 hours on days 1, 4, 8, and 11. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AT7519M 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 during course 1. Once the MTD has been
determined, up to 8 additional patients are treated at the MTD.

Patients undergo blood collection periodically for pharmacokinetic studies. Patients treated
at the MTD also undergo tumor tissue biopsies or aspirates and blood collection periodically
for additional pharmacodynamic and correlative biomarker studies.

After completion of study therapy, patients are followed at 4 weeks. Patients with complete
response, partial response, or stable disease are followed every 3 months thereafter until

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed diagnosis of 1 of the following:

- Advanced and/or metastatic solid tumor

- No more than 3 prior regimens for metastatic disease

- Refractory non-Hodgkin's lymphoma

- Clinically or radiologically documented disease

- Patients whose only evidence of disease is tumor marker elevation are not

- No untreated brain or meningeal metastases

- Patients with radiologic or clinical evidence of stable, treated brain
metastases are eligible provided they are asymptomatic AND have no requirement
for corticosteroids


- ECOG performance status 0-2

- Absolute granulocyte count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50

- Bilirubin normal

- ALT and AST ≤ 2 times ULN (5 times ULN if patient has documented liver metastases)

- Potassium normal

- Calcium normal

- Creatine kinase (CK or CPK) ≤ 2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction,
including any of the following:

- Significant cardiac event (including symptomatic heart failure or angina) within
the past 3 months or any cardiac disease that, in the opinion of the
investigator, increases the risk for ventricular arrhythmia

- Any history of ventricular arrhythmia, which was symptomatic or required
treatment (CTC grade 3), including multifocal PVCs, bigeminy, trigeminy, or
ventricular tachycardia

- Uncontrolled hypertension

- Previous history of QT prolongation with other medication

- Congenital long QT syndrome

- QT and QTc, with Bazett's correction, unmeasurable or ≥ 460 msec on screening

- LVEF < 45 % by MUGA for patients with significant cardiac history (i.e.,
myocardial infarction, severe hypertension, or arrhythmia) or prior doxorubicin
(> 450 mg/m²)

- No active or uncontrolled infections

- No serious illness or medical condition that would preclude study compliance

- No peripheral neuropathy > grade 1


- See Disease Characteristics

- At least 21 days since prior cytotoxic chemotherapy and recovered (solid tumors)

- At least 21 days since prior palliative radiotherapy and recovered

- Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy

- Prior hormonal, immunologic, biologic, or signal transduction inhibitor therapy

- At least 14 days since prior major surgery and recovered (no nonhealing wounds)

- At least 4 weeks since prior steroids

- No other concurrent medications which affect QT/QTc and cannot be discontinued

- No other concurrent experimental drugs or anticancer therapy

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose as assessed by NCI CTCAE v.30

Outcome Time Frame:

from time of 1st dose

Safety Issue:


Principal Investigator

Sebastien Hotte, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Margaret and Charles Juravinski Cancer Centre


Canada: Health Canada

Study ID:




Start Date:

August 2006

Completion Date:

January 2013

Related Keywords:

  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent adult grade III lymphomatoid granulomatosis
  • adult nasal type extranodal NK/T-cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin