- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00077558
3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome
A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias
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.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
OBJECTIVES:
- Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes.
- Determine the toxic effects of this regimen in these patients.
- Determine the maximum tolerated dose of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.
Cohorts of 3-6 patients receive escalating doses of fludarabine 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. Once the MTD is determined, 10 additional patients are treated at that dose level.
- Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours on day 1. Beginning within 4 hours after completion of 3-AP, patients receive fludarabine IV over 30 minutes on days 2-6.
In both groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.
Studietype
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
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Georgia
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Atlanta, Georgia, Forente stater, 30342-4777
- Blood and Marrow Transplant Group of Georgia
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Maryland
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Baltimore, Maryland, Forente stater, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, Forente stater, 21201
- Greenebaum Cancer Center at University of Maryland Medical Center
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Texas
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Houston, Texas, Forente stater, 77030-4095
- M.D. Anderson Cancer Center at University of Texas
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
- refraktær anemi med overflødig blaster
- kronisk myelomonocytisk leukemi
- tidligere behandlede myelodysplastiske syndromer
- sekundære myelodysplastiske syndromer
- akutt myeloid leukemi hos voksne med 11q23 (MLL) abnormiteter
- akutt myeloid leukemi hos voksne med inv(16)(p13;q22)
- akutt myeloid leukemi hos voksne med t(15;17)(q22;q12)
- akutt myeloid leukemi hos voksne med t(16;16)(p13;q22)
- akutt myeloid leukemi hos voksne med t(8;21)(q22;q22)
- sekundær akutt myeloid leukemi
- tilbakevendende akutt myeloid leukemi hos voksne
- atypisk kronisk myeloid leukemi
- myelodysplastisk/myeloproliferativ sykdom, ikke klassifiserbar
- akutt erytroid leukemi hos voksne (M6)
- akutt megakaryoblastisk leukemi hos voksne (M7)
- akutt minimalt differensiert myeloid leukemi (M0) hos voksne
- akutt monoblastisk leukemi hos voksne (M5a)
- akutt monocytisk leukemi hos voksne (M5b)
- akutt myeloblastisk leukemi hos voksne med modning (M2)
- voksen akutt myeloblastisk leukemi uten modning (M1)
- akutt myelomonocytisk leukemi hos voksne (M4)
- akutt basofil leukemi hos voksne
- akutt eosinofil leukemi hos voksne
- blastisk fase kronisk myelogen leukemi
- tilbakefallende kronisk myelogen leukemi
- refraktær kronisk lymfatisk leukemi
- tilbakevendende akutt lymfatisk leukemi hos voksne
- prolymfocytisk leukemi
- akselerert fase kronisk myelogen leukemi
- akutt promyelocytisk leukemi hos voksne (M3)
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Neoplasmer etter histologisk type
- Neoplasmer
- Sykdom
- Benmargssykdommer
- Hematologiske sykdommer
- Forstadier til kreft
- Syndrom
- Myelodysplastiske syndromer
- Leukemi
- Preleukemi
- Myeloproliferative lidelser
- Myelodysplastiske-myeloproliferative sykdommer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Fludarabin
- Fludarabinfosfat
Andre studie-ID-numre
- CDR0000352322, J0357
- P30CA006973 (U.S. NIH-stipend/kontrakt)
- U01CA070095 (U.S. NIH-stipend/kontrakt)
- JHOC-J0357
- NCI-6255
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