Back to resultsGTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia
Primary Purpose
Acute Undifferentiated Leukemia, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GTI-2040
pharmacological study
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Acute Undifferentiated Leukemia
Eligibility 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
Sites / Locations
- City of Hope Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.
Outcomes
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)
Change in dCTP levels in PBMC and bone marrow by Real-Time PCR
Secondary Outcome Measures
Objective tumor response
Overall survival
Time to failure
Duration of response
Change in expression levels of R1, R2, and p53R2 mRNA in PBMC by Real-Time PCR
Change in intracellular levels of GTI-2040 by ELISA
Incidence of grade 3 or higher toxicity assessed by CTCAE v3.0
Full Information
NCT ID
NCT00459212
First Posted
April 9, 2007
Last Updated
December 3, 2015
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00459212
Brief Title
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
Official Title
Phase I and Pharmacodynamic Study of GTI-2040 (NSC 722929, IND 67368) in Acute Leukemias
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.
Intervention Type
Drug
Intervention Name(s)
GTI-2040
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative study
Intervention Type
Procedure
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative study
Primary Outcome Measure Information:
Title
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
Title
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 Measure Information:
Title
Objective tumor response
Time Frame
Up to 3 years
Title
Overall survival
Time Frame
Up to 3 years
Title
Time to failure
Time Frame
Up to 3 years
Title
Duration of response
Time Frame
Up to 3 years
Title
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
Title
Change in intracellular levels of GTI-2040 by ELISA
Time Frame
Day 1, 4, 15, and 19 of course 1
Title
Incidence of grade 3 or higher toxicity assessed by CTCAE v3.0
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Kirschbaum
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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