Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults
Information source: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Lymphoblastic Leukemia
Intervention: Clofarabine, Cyclophosphamide (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Gruppo Italiano Malattie EMatologiche dell'Adulto Official(s) and/or principal investigator(s): Renato BASSAN, Pr., Principal Investigator, Affiliation: U.O. di Ematologia- Ospedale dell'Angelo - Mestre
Overall contact: Paola Fazi, Dr., Email: p.fazi@gimema.it
Summary
This is a multicentric, prospective pilot trial testing a Clofarabine-Cyclophosphamide
combination to treat refractory and first bone marrow relapse adult ALL, for the achievement
of a complete remission (CR) and the concurrent evaluation of biological response in ALL
cells (minimal residual disease, apoptosis and DNA cell damage, pharmacogenomics).
Clinical Details
Official title: "A Phase II Study With a Sequential Clofarabine-cyclophosphamide Combination Schedule as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) in Adult Patients"
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The primary end-point is the rate of patients in CR after induction therapy.
Secondary outcome: Number of participants with toxicity of grade 2 or greater (CTCAE version 4.0) eventsRate of ALL blast cells in apoptosis and DNA damage per patient induced by Clofarabine when used in combination with Cyclophosphamide. Number of participants with minimal residual disease (MRD) response in remission. Disease-free survival (DFS) Overall Survival (OS). Cumulative incidence of relapse (CIR). Rate of Disease free survival (DFS) in very high risk and high risk patients Rate of Overall Survival (OS) in very high risk and high risk patients Rate of Cumulative Incidence of Relapse (CIR) in very high risk and high risk patients
Detailed description:
The proposed treatment schedule consists of a combination of Clofarabine plus
Cyclophosphamide administered over 5 consecutive days (Treatment scheme). This is an open,
nonrandomized prospective phase II trial aimed to evaluating (1) activity of this
combination in terms of CR rate.
- STEP 1. All eligible patients will be screened for the availability of an HLA-matched
or partially mismatched compatible HSCT donor, of both family related - or unrelated
type (early activation required), including cord blood and haploidentical siblings.
Moreover, pre-treatment investigation will include collection and storage of patient
ALL cells for specific biological studies relating to sensitivity and response to study
chemotherapeutic combination.
- STEP 2. Cycle 1 will be applied to all eligible patients once all enrollment criteria
are confirmed.
- STEP 3. After cycle 1, response will be evaluated.
- STEP 4. After remission induction cycle 1, only responsive patients (CR or PR, see
below for definitions) could be given cycle 2, according to the opinion of the
responsible physician and with a minimum intercycle interval of 4 weeks from day 1 of
cycle 1. All NR patients will be declared off study and will not be given a second
course with study combination. The suggested treatment following cycle 2 (or cycle 1 if
cycle 2 is omitted) is HSCT.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Signed written informed consent according to IGH/EU/GCP and national local laws.
- Age 18-60 years.
- ALL with B-/T-precursor phenotype refractory to first line therapy.
- ALL with B-/T-precursor phenotype 1st isolated bone marrow relapse, occurring < 24
months from the achievement of first CR, after chemotherapy or hematopoietic
stem-cell transplantation (HSCT) defined as follows:
* ≥ 5% leukemic blasts in the bone marrow not attributable to another cause (e. g.
marrow regeneration); if there are no circulating blasts and the bone marrow contain
5-20% leukemic blasts, a repeat bone marrow performed at least a week later is
necessary to confirm relapse.
- ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of
complications.
- Adequate hepatic and renal function, unless considered due to organ leukemic
involvement:
- Serum creatinine <1. 5 mg/dl; if serum creatinine >1. 5 mg/dl, then the estimated
glomerular filtration rate (GFR) must be > 60 mL/min/1. 73 m2 as calculated by
the Modification of Diet in Renal Disease equation where Predicted GFR
(ml/min/1. 73 m2) = 186 x (Serum Creatinine)-1. 154 x (age in years)-0. 023 x
(0. 742 if patient is female), x (1. 212) if patient is black.
- Serum bilirubin ≤ 1. 5 x upper limit of normal (ULN).
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2. 5 x ULN.
- Alkaline phosphatase ≤ 2. 5 x ULN.
Exclusion Criteria:
- Prior exposure to Clofarabine or, in primary refractory patients only, to
Cyclophosphamide during induction courses.
- Patients relapsed > 24 months from first CR. - Philadelphia chromosome-positive (Ph+)
ALL.
- Diagnosis of Burkitt-type/B-ALL, or B-/T-lymphoblastic lymphoma with < 25% bone
marrow involvement.
- Concurrent or isolated central nervous system (CNS) relapse.
- Pre-existing, uncontrolled pathology such as cardiac disease (congestive/ischemic,
acute myocardial infarction within the past 3 months, untreatable arrythmias, NYHA
classes III and IV).
- Severe neurological or psychiatric disorder that impairs the patient's ability to
understand and sign the informed consent, or to cope with the intended treatment
plan.
- Active uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment).
- HIV positive serology or active hepatitis infection. - Concurrent diagnosis of active
cancer requiring concurrent chemotherapy and/or radiotherapy, and/or with life
expectancy < 1 year.
- Patients who are pregnant or adults of reproductive potential not employing an
effective method of birth control (women of childbearing potential must have a
negative serum pregnancy test within 48 hrs prior to administration of
Clofarabine-Cyclophosphamide). Post menopausal women must be amenorrheic for at least
12 months to be considered of non-childbearing potential. Male and female patients
must agree to employ an effective barrier method of birth control throughout the
study and for up to 3 months following discontinuation of study drugs.
Locations and Contacts
Paola Fazi, Dr., Email: p.fazi@gimema.it
Unità Operativa Ematologia 1 - Università degli Studi di Bari, Bari 70010, Italy; Recruiting Giorgina SPECCHIA, Pr. Giorgina SPECCHIA, Pr., Principal Investigator Domenico PASTORE, Pr., Sub-Investigator
Divisione di Ematologia - Ospedali Riuniti, Bergamo, Italy; Recruiting Alessandro Rambaldi, Pr. Alessandro Rambaldi, Pr., Principal Investigator
Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi, Bologna, Italy; Recruiting Giovanni Martinelli, Pr. Giovanni Martinelli, Pr., Principal Investigator Antonio Curti, Dr., Sub-Investigator
Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO, Bolzano, Italy; Not yet recruiting Vincenzo CASSIBBA, Dr. Vincenzo CASSIBBA, Dr., Principal Investigator Sergio CORTELAZZO, Dr., Sub-Investigator
Sezione di Ematologia e Trapianti Spedali Civili, Brescia 21125, Italy; Recruiting Giuseppe ROSSI Giuseppe ROSSI, Pr., Principal Investigator Erika BORLENGHI, Dr., Sub-Investigator
Azienda ASL di Cagliari, Cagliari 9121, Italy; Not yet recruiting Claudio ROMANI, Dr. Claudio ROMANI, Dr., Principal Investigator Martina Pettinau, Dr., Principal Investigator
Ospedale Santa Croce Divisione di Ematologia Cuneo, Cuneo, Italy; Active, not recruiting
Policlinico di Careggi, Università delgi studi di Firenze, Firenze, Italy; Not yet recruiting Alberto BOSI Alberto BOSI, Dr., Principal Investigator Giacomo GIANFALDONI, Dr., Sub-Investigator
Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST, Meldola, Italy; Recruiting Maria Benedetta Giannini Maria Benedetta Giannini, Principal Investigator
U.O. di Ematologia- Ospedale dell'Angelo - Mestre, Mestre, Venezia, Italy; Recruiting Renato BASSAN, Pr. Renato BASSAN, Pr., Principal Investigator
U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele, Milano, Italy; Recruiting Fabio Ciceri, Dr. Fabio Ciceri, Dr., Principal Investigator Stefania Trinca, Dr., Sub-Investigator
UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico, Milano, Italy; Recruiting Giorgio Lambertenghi, Pr. Giorgio Lambertenghi, Pr., Principal Investigator
Centro Oncologico Modenese - Dipartimento di Oncoematologia, Modena, Italy; Not yet recruiting Mario LUPPI, Dr. Mario LUPPI, Dr., Principal Investigator Monica MORSELLI, Dr., Sub-Investigator
N. Osp. divisione di Ematologia "S.Gerardo dei Tintori", Monza, Italy; Recruiting Enrico Maria POGLIANI, Dr. Enrico Maria POGLIANI, Dr., Principal Investigator Monica FUMAGALLI, Dr., Sub-Investigator
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli", Napoli, Italy; Not yet recruiting Felicetto Ferrara, Dr Felicetto Ferrara, Dr., Principal Investigator
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia, Napoli, Italy; Not yet recruiting Fabrizio Pane, Pr. Fabrizio Pane, Pr., Principal Investigator
Ospedale Cervello, Palermo 90146, Italy; Recruiting Francesco FABBIANO, Email: ffabbiano@libero.it Francesco FABBIANO, Pr., Principal Investigator Rosaria FELICE, Dr., Sub-Investigator
U.O. Ematologia Clinica - Azienda USL di Pescara, Pescara 65100, Italy; Recruiting Giuseppe FIORITONI, Pr. Anna RECCHIA Giuseppe FIORITONI, Pr., Principal Investigator Anna RECCHIA, Dr., Sub-Investigator
Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia, Pisa, Italy; Recruiting Mario Petrini Mario Petrini, Principal Investigator
Dipartimento Oncologico - Ospedale S.Maria delle Croci, Ravenna, Italy; Recruiting Eliana Zuffa Eliana Zuffa, Principal Investigator Alessandra D'Addio, Sub-Investigator
Calabria Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli", Reggio Calabria, Italy; Recruiting Francesco Nobile, Pr. Francesco Nobile, Pr., Principal Investigator Francesca Ronco, Dr., Sub-Investigator
Complesso Ospedaliero S. Giovanni Addolorata, Roma, Italy; Not yet recruiting Luciana Annino, Pr. Luciana Annino, Pr., Principal Investigator
Umberto I di Roma - Dipartimento di Biotecnologie Cellulari ed Ematologia, Roma 00161, Italy; Recruiting Roberto Foà Roberto Foà, Principal Investigator Giovanna Meloni, Dr., Sub-Investigator
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia, Roma, Italy; Recruiting Roberto Foà, Pr. Roberto Foà, Pr., Principal Investigator Giovanna Meloni, Pr., Sub-Investigator
Università degli Studi - Policlinico di Tor Vergata, Roma, Italy; Recruiting Sergio Amadori, Pr. Sergio Amadori, Pr., Principal Investigator Adriano Venditti, Pr., Sub-Investigator
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Recruiting Nicola CASCAVILLA Nicola CASCAVILLA, Pr., Principal Investigator Lorella MELILLO, Dr., Sub-Investigator
SCDO Ematologia 2 AOU Giovanni Battista, Torino, Italy; Recruiting Ernesta AUDISIO, Dr. Ernesta AUDISIO, Principal Investigator Filippo MARMONT, Dr., Sub-Investigator
Additional Information
GIMEMA Foundation Website
Starting date: October 2012
Last updated: May 26, 2015
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