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"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" GIMEMA Protocol LAL1610, EudraCT Number 2010-019742-12

Phase 2
18 Years
60 Years
Not Enrolling
Acute Lymphoblastic Leukemia

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Trial Information

"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" GIMEMA Protocol LAL1610, EudraCT Number 2010-019742-12

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.

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

- Adequate hepatic and renal function, unless considered due to organ leukemic

- 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+)

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary end-point is the rate of patients in CR after induction therapy.

Outcome Description:

Disappearance of any clinical and laboratoristic sign of ALL. The patient must be transfusion-free with neutrophils >1.0 x109/L and platelets >100 x109/L. BM examination must show absence or reduction of blast cell content (< 5%, none of which obviously leukemic), with cellularity in the normal or slightly hypocellular range and with evidence of trilineage hemopoiesis. BM is examined on day 28 from start of chemotherapy cycle 1, or later as clinically indicated in ill/cytopenic patients, and after cycle 2 in patients with PR proceeding to this treatment.

Outcome Time Frame:

At day +28 from start of chemotherapy cycle 1 and after cycle 2 in pts with PR

Safety Issue:


Principal Investigator

Renato BASSAN, Pr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

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


Italy: Ethics Committee

Study ID:




Start Date:

July 2012

Completion Date:

July 2015

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Adult patients
  • Refractory
  • Relapsed
  • clofarabine
  • cyclophosphamide
  • refractory and relapsed acute lymphoblastic leukemia
  • ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma