NCT00077558

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2004

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

February 10, 2004

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 12, 2004

Completed
Last Updated

March 10, 2010

Status Verified

March 1, 2010

First QC Date

February 10, 2004

Last Update Submit

March 9, 2010

Conditions

LeukemiaMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative Diseases

Keywords

accelerated phase chronic myelogenous leukemiablastic phase chronic myelogenous leukemiarelapsing chronic myelogenous leukemiapreviously treated myelodysplastic syndromessecondary myelodysplastic syndromesrefractory chronic lymphocytic leukemiarecurrent adult acute lymphoblastic leukemiaprolymphocytic leukemiarefractory anemia with excess blastschronic myelomonocytic leukemiarecurrent adult acute myeloid leukemiasecondary acute myeloid leukemiaadult acute minimally differentiated myeloid leukemia (M0)adult acute monocytic leukemia (M5b)adult acute erythroid leukemia (M6)adult acute megakaryoblastic leukemia (M7)adult acute myeloblastic leukemia with maturation (M2)adult acute myeloblastic leukemia without maturation (M1)adult acute myelomonocytic leukemia (M4)adult acute monoblastic leukemia (M5a)adult acute promyelocytic leukemia (M3)adult acute eosinophilic leukemiaadult acute basophilic leukemiaatypical chronic myeloid leukemiamyelodysplastic/myeloproliferative disease, unclassifiableadult acute myeloid leukemia with t(8;21)(q22;q22)adult acute myeloid leukemia with t(16;16)(p13;q22)adult acute myeloid leukemia with inv(16)(p13;q22)adult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult acute myeloid leukemia with t(15;17)(q22;q12)

Interventions

fludarabine phosphateDRUG
triapineDRUG

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia * International Prognostic Scoring System (IPSS) score at least 1.5 based on the following: * More than 10% marrow blasts * Cytopenias in at least 2 lineages * Adverse cytogenetics * Acute myeloid leukemia (AML) * All subtypes, including MDS/AML and treatment-related (secondary) AML * Acute lymphoblastic leukemia * Acute progranulocytic leukemia * Ineligible for arsenic therapy * Chronic myelogenous leukemia * Accelerated phase or blastic crisis * Chronic lymphocytic leukemia * Prolymphocytic leukemia * Received or ineligible for established curative regimens, including stem cell transplantation * Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * No history of hemolytic anemia grade 2 or greater * No known glucose-6-phosphate dehydrogenase (G6PD) deficiency * G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry) Hepatic * SGOT and SGPT no greater than 2.5 times normal * Bilirubin no greater than 2 mg/dL * No chronic hepatitis Renal * Creatinine normal OR * Creatinine clearance at least 60 mL/min Cardiovascular * No active heart disease * No myocardial infarction within the past 3 months * No severe coronary artery disease * No arrhythmias (other than atrial flutter or fibrillation) requiring medication * No uncontrolled congestive heart failure Pulmonary * No dyspnea at rest or with minimal exertion * No severe pulmonary disease requiring supplemental oxygen Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No neuropathy grade 2 or greater * No active uncontrolled infection * Infections under active treatment and controlled by antibiotics are allowed * No other life-threatening illness * No psychiatric illness that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim \[G-CSF\], sargramostim \[GM-CSF\], interleukin-3, and interleukin-11) * No concurrent immunotherapy Chemotherapy * Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects) * At least 72 hours since prior hydroxyurea * At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas) * No more than 12 prior courses of fludarabine * No more than 3 prior cytotoxic chemotherapy regimens * No other concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * At least 2 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * Not specified Other * At least 1 week since prior non-myelosuppressive treatment * No more than 4 prior induction regimens * No other concurrent therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (4)

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342-4777, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4095, United States

Location

Related Publications (1)

  • Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leuk Res. 2008 Jan;32(1):71-7. doi: 10.1016/j.leukres.2007.05.003. Epub 2007 Jul 20.

    PMID: 17640728RESULT

MeSH Terms

Conditions

LeukemiaMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesLeukemia, Myeloid, Accelerated PhaseBlast CrisisLeukemia, Lymphocytic, Chronic, B-CellPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, ProlymphocyticAnemia, Refractory, with Excess of BlastsLeukemia, Myelomonocytic, ChronicLeukemia, Myeloid, AcuteLeukemia, Monocytic, AcuteLeukemia, Erythroblastic, AcuteLeukemia, Megakaryoblastic, AcuteLeukemia, Myelomonocytic, AcuteLeukemia, Promyelocytic, AcuteLeukemia, Eosinophilic, AcuteLeukemia, Basophilic, AcuteLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeMyeloproliferative DisordersCongenital Abnormalities

Interventions

fludarabine phosphate3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesAnemia, RefractoryAnemiaCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Judith E. Karp, MD

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Purpose
TREATMENT
Sponsor Type
OTHER

Study Record Dates

First Submitted

February 10, 2004

First Posted

February 12, 2004

Study Start

January 1, 2004

Last Updated

March 10, 2010

Record last verified: 2010-03

Locations

US(4)