Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults

NCT ID: NCT01462253

Last Updated: 2019-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2017-03-11

Brief 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).

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clofarabine, Cyclophosphamide

Clofarabine concentrate for solution for infusion should be filtered using a 0.2 micron filter and diluted to a final concentration between 0.15 mg/mL and 0.4 mg/mL with 0.9% sodium chloride injection USP or European Pharmacopeia (EP) normal saline (NS), or 5% dextrose injection (D5W) USP or EP prior to infusion.

Cyclophosphamide should be prepared for parenteral use by adding 0.9% sterile sodium chloride solution. Solutions of cyclophosphamide may be injected intravenously without further dilution or may be infused following further dilution: Dextrose Injection, USP (5% dextrose), Dextrose and Sodium Chloride Injection, USP (5% dextrose and 0.9% sterile sodium chloride), 5% Dextrose and Ringer's Injection.

Group Type: EXPERIMENTAL

Clofarabine, Cyclophosphamide

Intervention Type: DRUG

The proposed treatment schedule consists of a combination of Clofarabine plus Cyclophosphamide administered over 5 consecutive days (Treatment scheme).

Interventions

Clofarabine, Cyclophosphamide

The proposed treatment schedule consists of a combination of Clofarabine plus Cyclophosphamide administered over 5 consecutive days (Treatment scheme).

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renato BASSAN, Pr.

Role: PRINCIPAL_INVESTIGATOR

U.O. di Ematologia- Ospedale dell'Angelo - Mestre

Locations

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, , Italy

Divisione di Ematologia - Ospedali Riuniti

Bergamo, , Italy

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

Bologna, , Italy

Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO

Bolzano, , Italy

Sezione di Ematologia e Trapianti Spedali Civili

Brescia, , Italy

Azienda ASL di Cagliari

Cagliari, , Italy

Ospedale Santa Croce Divisione di Ematologia Cuneo

Cuneo, , Italy

Policlinico di Careggi, Università delgi studi di Firenze

Florence, , Italy

Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

Meldola, , Italy

U.O. di Ematologia- Ospedale dell'Angelo - Mestre

Mestre, , Italy

U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele

Milan, , Italy

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, , Italy

Centro Oncologico Modenese - Dipartimento di Oncoematologia

Modena, , Italy

N. Osp. divisione di Ematologia "S.Gerardo dei Tintori"

Monza, , Italy

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, , Italy

Ospedale Cervello

Palermo, , Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia

Pisa, , Italy

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, , Italy

Calabria Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, , Italy

Umberto I di Roma - Dipartimento di Biotecnologie Cellulari ed Ematologia

Roma, , Italy

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, , Italy

Università degli Studi - Policlinico di Tor Vergata

Roma, , Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

SCDO Ematologia 2 AOU Giovanni Battista

Torino, , Italy

Countries

Italy

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

http://www.gimema.it/en/index.php

GIMEMA Foundation Website

Other Identifiers

LAL1610

Identifier Type: -

Identifier Source: org_study_id