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: April 9, 2013
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 ] [ Designated as safety issue: Yes ]
  • Change in dCTP levels in PBMC and bone marrow by Real-Time PCR [ Time Frame: Days 1, 4, 15, and 19 of course 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective tumor response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time to failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in intracellular levels of GTI-2040 by ELISA [ Time Frame: Day 1, 4, 15, and 19 of course 1 ] [ Designated as safety issue: No ]
  • Incidence of grade 3 or higher toxicity assessed by CTCAE v3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

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
Genders Eligible for Study:   Both
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
Investigators
Principal Investigator: Mark Kirschbaum City of Hope Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459212     History of Changes
Other Study ID Numbers: NCI-2009-00206, PHI-57, CDR0000539257, U01CA062505
Study First Received: April 9, 2007
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 28, 2014