Clinical trial NCT00419081: Study of Forodesine Hydrochloride in Patients With Relapsed/Refractory Precursor T-Lymphoblastic Leukemia/Lymphoma Who Have Failed Two or More Prior Treatment Regimens
Official title: A Phase IIb, Multicenter, Open-Label, Nonrandomized, Repeat-Dose Study of Forodesine Hydrochloride in Patients With Relapsed/Refractory Precursor T-Lymphoblastic Leukemia/Lymphoma Who Have Failed Two or More Prior Treatment Regimens.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: leukemia
lymphoma
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-01-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Forodesine Hydrochloride is effective in treating patients with relapsed/refractory precursor T-Lymphoblastic Leukemia/Lymphoma who have failed two or more prior treatment regimens.


Eligibility criteria: Inclusion Criteria:

* Patients with an unequivocal histologic diagnosis of precursor T-lymphoblastic leukemia/lymphoma (World Health Organization \[WHO\] classification).
* Failure to have responded to or relapsed after two or more treatment regimens for their disease, one of which could be HSCT.
* Performance status of 2 by Eastern Cooperative Oncology Group (ECOG) criteria (see Appendix A).
* Eighteen years of age and older.
* Life expectancy of at least three months.
* Adequate liver function (aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\] ≤3 times upper limit of normal), unless related to the underlying leukemia.
* Negative serum or urine pregnancy test within two to seven days prior to the start of study treatment in females of childbearing potential.
* Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study in such a manner that the risk of pregnancy is minimized. Acceptable contraceptives include intra-uterine devices (IUDs), hormonal contraceptives (oral, depot, patch, or injectable), and double-barrier methods such as condoms or diaphragms with spermicidal gel or foam.
* Signed informed consent form (ICF) prior to start of any study-specific procedures.
* Willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act (HIPAA) policy (U.S. patients only).

Exclusion Criteria:

* Patients with known human immunodeficiency virus (HIV) infection or human T lymphotrophic virus 1 (HTLV-1).
* Patients with active hepatitis B or C infection.
* Patients with clinical evidence of active central nervous system (CNS) leukemia.
* Active serious infection not controlled by oral or intravenous antibiotics.
* Patients with a calculated creatinine clearance of \<50 mL/min.
* Prior treatment with any investigational antileukemic or chemotherapy agent within seven days prior to study entry or lack of full recovery from side effects due to prior therapy, independent of when that therapy was given.
* Rapidly progressive disease with compromised organ function judged to be life threatening by the Investigator.
* Concurrent treatment with other antileukemia agents (CNS prophylaxis \[e.g., intrathecal methotrexate, cytarabine, or hydrocortisone\] and corticosteroid use will not be excluded, but must first be approved by the Medical Monitor) (see Sections 9.2.1 and 9.2.2).
* Pregnant and/or lactating female.
* Patients who cannot swallow or who have chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the product.
* Hypersensitive or intolerant to any component of the study drug formulations.
* Patients who have received prior forodesine treatment.

Primary outcomes:
measure: To determine the rate of complete remission for T lymphoblastic leukemia/lymphoma relapsed or refractory patients. The complete remission rate will be evaluated over the three-month Initial Treatment Period.
Secondary outcomes:
measure: To determine the rate of CR achieved based on prior HSCT status
measure: Assess safety and tolerability
measure: Assess survival end points
measure: Evaluate the maintenance and duration of response
measure: Evaluate the proportion of patients able to proceed to HSCT
measure: Evaluate the effects of this forodesine regimen on plasma levels of dGuo
measure: Determine the effects of this forodesine regimen on clinical end points
measure: Explore potential predictive biomarkers
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Shreveport
country: United States
facility: Louisana State University Health Sciences Center
state: Louisiana
city: Valhalla
country: United States
facility: New York Medical College Division of Oncology
state: New York
city: Columbia
country: United States
facility: Liberty Hematology and Oncology
state: South Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Faculdade de Medicina do ABC
name: Auro del Giglio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital das Clinicas de Faculdade de Medicina de Ribeirao Preto
name: Belinda Pinto Simoes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Irmandade da Santa Casa de Misercordia de Sao Paulo
name: Carlos Sergio Chiattone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Clinicias da UICAMP - Centro de Hematologia e Hemoterapia
name: Carmino Antonio de Souza, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Goiano de Oncologia
name: David Barqueti Jendiroba, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INCA - Instituto Nacional de Cancer
name: Ernesto de Meis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Estadual de Hematologia Artur de Siqueira Cavalcanti - HEMORIO
name: Fernando Antonio Sellos Ribeiro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Nossa Senhora de Conceicao
name: Ines Guterres, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Erasto Gaertner - Liga Paranaense de Combate ao Cancer - CEPEP
name: Johnny Francisco Cordeiro Camargo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Santa Marcelina
name: Jose Salvador Rodrigues Oliveira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Clinicas de Porto Alegre
name: Lucia Mariano da Rocha Silla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacao Hospital Amaral Carvalho
name: Mair Pedro de Souza, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Brigadeiro
name: Maria Aparecida Zanichelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Oncologia Pediatrica - GRAACC Grupo de Apoio as Adolescente e a Crianca com Cancer - UNIFESP
name: Maria Lucia de Martino Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Clinicas da Universidade Federal do Parana
name: Ricardo Pasquini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Haematology
name: Nicholas Novitzky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Free State University
name: Vernon Louw, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Farhad Ravandi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Medical College, Division of Oncology
name: Karen Seiter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Louisana State University Health Sciences Center
name: Francesco Turturro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Luis Isola, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago Hospital
name: Wendy Stock, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Liberty Hematology and Oncology
name: Francisco Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: James Foran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Ellen Ritchie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Emory Clinic
name: Leonard Heffner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Vanderbilt University Medical Center
name: Madan Jagasia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Katarzyna Jamieson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Gary Schiller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Anjali Advani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Kellie Sprague, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Tanya Trippett, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Roswell Park Cancer Institute
name: Meir Wetzler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University Hospital
name: Alexander Gaiger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Heamtology
name: Werner Linkersch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Heamatology
name: David Nachbaur, MD
role: PRINCIPAL_INVESTIGATOR
name: Agnes Buzin, MD
role: PRINCIPAL_INVESTIGATOR
name: Stephane de Botton, MD
role: PRINCIPAL_INVESTIGATOR
name: Jacques Delaunnay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Clinique des Maladies du Sang
name: Herve Dombret, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service d'Hematologie
name: Francoise Huguet-Rigal, MD
role: PRINCIPAL_INVESTIGATOR
name: Norbert Ifrah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU du Hart Leveque
name: Arnaud Pigneux, MD
role: PRINCIPAL_INVESTIGATOR
name: Bruno Quesnel, MD
role: PRINCIPAL_INVESTIGATOR
name: Houmedaly Reman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maladies du Sang
name: Xavier Thomas, MD
role: PRINCIPAL_INVESTIGATOR
name: Norbert Vey, MD
role: PRINCIPAL_INVESTIGATOR
name: Francis Witz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute for Heamatology & Transfusiology
name: Genadi Iosava, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heamatology and Transfusiology Dept
name: Mamia Zodelava, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitat Regensburg
name: Reinhard Andreesen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Innere Abt. II
name: Walter Aulitzky, MD
role: PRINCIPAL_INVESTIGATOR
name: Ulrich Duehrsen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum Carl Gustav Carus der Technischen Universitat
name: Gerhard Ehninger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ABT Hamatologie und Onkologie
name: Arnold Ganser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitatsklinik Dusseldorf
name: R. Haas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiterin der Studienzentrale
name: Dieter Hoelzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite Universitatsmedizin Berlin
name: W-D Ludwig, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Abt. Haematologie / Onkologie
name: Deiter Niederwieser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medizinische Klinik I
name: Michael Pfreunschuh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Innere Medizin III, Hamatologie und Onkologie
name: Mathias Schmid, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamatologsiche Abteilung
name: Norbert Schmitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Med. Klinik I / Hamatolgie
name: Peter Staib, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Innere Medizin A
name: Matthias Stelljes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istitutp di Ematologia ed Oncologia Medica
name: Michele Baccarani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dipartimento di Oncoloia ed Ematico
name: Renato Bassan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aziendo Osperdaliero Universitaria Careggi Oncologia
name: Alberto Bosi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Antonio Cardarelli
name: Felicetto Ferrara, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cattedra di Ematologie
name: Roberto Foa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Divisione di Ematologia
name: Eugenio Gallo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UO Universita degi Studi Policinico Ematologia
name: Vincenzo Liso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Osperdaliera Vincenzo Cervello Divisione
name: Salvatore Mirto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Complessa di Ematologia and Dir Departmento
name: Enrica Morra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ematologia
name: Enrico Pogliani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eramus University Medical Centre
name: Bob Lowenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Hematologii I
name: Jerzy Holowiecki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Hematologii i Onkologii
name: Wieslaw Jedrzejczak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Heamatology
name: Kazimierz Kuliczkowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Hematologii Akademii Meduycznej Wojewodzki
name: Tadeusz Robak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Katedra i Klinika Hematologii Collegium Medicum
name: Aleksander Skotnicki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Hematology Clinic
name: K. Abdulkadyrov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Clinical Heam and Immunotherapy Dept.
name: Anatoli Golenkov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculty Therapy Dept
name: S. Moiseev, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dir. Research Institute for BMT and Molecular Hematology
name: Valerie Savchenko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Insitut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
name: J. Ribera, MD
role: PRINCIPAL_INVESTIGATOR
References: