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GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00459212
First received: April 9, 2007
Last updated: December 3, 2015
Last verified: April 2013
  Purpose
This phase I trial is studying the side effects and best dose of GTI-2040 in treating patients with relapsed, refractory, or high-risk acute leukemia, high-grade myelodysplastic syndromes, or refractory or blastic phase chronic myelogenous leukemia. Drugs used in chemotherapy, such as GTI-2040, work in different ways to stop the growth of cancer or abnormal cells, either by killing the cells or by stopping them from dividing.

Condition Intervention Phase
Acute Undifferentiated Leukemia 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 Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Drug: GTI-2040 Procedure: pharmacological study Procedure: laboratory biomarker analysis Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I and Pharmacodynamic Study of GTI-2040 (NSC 722929, IND 67368) in Acute Leukemias

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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) [ Time Frame: 28 days ]
  • Change in dCTP levels in PBMC and bone marrow by Real-Time PCR [ Time Frame: Days 1, 4, 15, and 19 of course 1 ]

Secondary Outcome Measures:
  • Objective tumor response [ Time Frame: Up to 3 years ]
  • Overall survival [ Time Frame: Up to 3 years ]
  • Time to failure [ Time Frame: Up to 3 years ]
  • Duration of response [ Time Frame: Up to 3 years ]
  • Change in expression levels of R1, R2, and p53R2 mRNA in PBMC by Real-Time PCR [ Time Frame: Day 1, 4, 15, and 19 of course 1 ]
  • Change in intracellular levels of GTI-2040 by ELISA [ Time Frame: Day 1, 4, 15, and 19 of course 1 ]
  • Incidence of grade 3 or higher toxicity assessed by CTCAE v3.0 [ Time Frame: Up to 3 years ]

Enrollment: 24
Study Start Date: March 2007
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.
Drug: GTI-2040
Given IV
Procedure: pharmacological study
Correlative study
Other Name: pharmacological studies
Procedure: laboratory biomarker analysis
Correlative study

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of GTI-2040 in patients with relapsed, refractory, or high-risk acute leukemia, high-grade myelodysplastic syndromes, or refractory or blastic phase chronic myelogenous leukemia.

II. Assess the toxicity and efficacy of this drug in these patients. III. Assess plasma and intracellular pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive GTI-2040 IV continuously on days 1-4 and 15-18. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of GTI-2040 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Blood samples are collected on days 1, 4, 15, and 19 of course 1 for pharmacokinetic studies. Samples are analyzed by proteomic assay, dCTP pool measurement, and real-time polymerase chain reaction for mRNA of RRM2, RRM1, and p53R2.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:

    • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to primary standard induction therapy
    • Relapsed or refractory acute leukemia
    • Chronic myelogenous leukemia (CML) in blast crisis at diagnosis OR that failed prior aggressive induction chemotherapy
  • Diagnosis of 1 of the following:

    • Acute leukemia secondary to preexisting hematologic condition or prior chemotherapy at diagnosis OR that failed prior aggressive induction chemotherapy
    • Advanced myelodysplastic syndromes (intermediate-1 or greater)
    • De novo acute leukemia (myeloid or nonmyeloid)
  • Not a candidate for aggressive standard induction chemotherapy
  • De novo AML or ALL (patients > 60 years of age)
  • No suspected or proven active CNS leukemia
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
  • Life expectancy >= 8 weeks
  • Bilirubin =< 1.5 mg/dL
  • AST and ALT < 3 times upper limit of normal (ULN)
  • Creatinine =< 1.5 times ULN
  • No HIV positivity
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to other phosphorothiolated oligonucleotides
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing, active, or poorly controlled infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Cardiac arrhythmia
    • Poorly controlled pulmonary disease
    • Psychiatric illness or social situation that would preclude study compliance
  • Recovered from all prior therapies
  • Prior autologous or allogeneic stem cell transplantation allowed (No active graft-vs-host disease > grade 2)
  • At least 2 weeks since prior and no concurrent cytotoxic chemotherapy
  • At least 2 weeks since prior and no concurrent biologic therapy
  • At least 2 weeks since any other prior investigational agent
  • No other concurrent anticancer therapy, including radiotherapy or hormonal therapy
  • Concurrent imatinib mesylate for CML allowed
  • Not pregnant or nursing
  • Negative pregancy test
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459212

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark Kirschbaum City of Hope Medical Center
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459212     History of Changes
Other Study ID Numbers: NCI-2009-00206
PHI-57
CDR0000539257
U01CA062505 ( U.S. NIH Grant/Contract )
Study First Received: April 9, 2007
Last Updated: December 3, 2015

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasm Metastasis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplastic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Cell Transformation, Neoplastic
Carcinogenesis

ClinicalTrials.gov processed this record on July 21, 2017