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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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 |
- 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 ]
- 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 |
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 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 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 May 21, 2013