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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) events

Rate 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

Page last updated: August 23, 2015

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