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Acute Lymphoblastic LeukemiaPhase 2LAL1610NCT01462253

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

A Phase 2 study testing Clofarabine, Cyclophosphamide in people with Acute Lymphoblastic Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 27 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Clofarabine, Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
27 sitesItaly
Study dates
Oct 2012to 11 Mar 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

Italy27 sites

  • Unità Operativa Ematologia 1 - Università degli Studi di Bari

    Bari, 70010

  • Divisione di Ematologia - Ospedali Riuniti

    Bergamo

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

    Bologna

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

    Bolzano

  • Sezione di Ematologia e Trapianti Spedali Civili

    Brescia, 21125

  • Azienda ASL di Cagliari

    Cagliari, 9121

  • Ospedale Santa Croce Divisione di Ematologia Cuneo

    Cuneo

  • Policlinico di Careggi, Università delgi studi di Firenze

    Florence

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

    Meldola

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

    Mestre

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

    Milan

  • UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

    Milan

  • Centro Oncologico Modenese - Dipartimento di Oncoematologia

    Modena

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

    Monza

  • Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

    Naples

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

    Naples

  • Ospedale Cervello

    Palermo, 90146

  • U.O. Ematologia Clinica - Azienda USL di Pescara

    Pescara, 65100

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

    Pisa

  • Dipartimento Oncologico - Ospedale S.Maria delle Croci

    Ravenna

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

    Reggio Calabria

  • Umberto I di Roma - Dipartimento di Biotecnologie Cellulari ed Ematologia

    Roma, 00161

  • Complesso Ospedaliero S. Giovanni Addolorata

    Roma

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

    Roma

  • Università degli Studi - Policlinico di Tor Vergata

    Roma

  • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

  • SCDO Ematologia 2 AOU Giovanni Battista

    Torino

Other trials in Italy

About this study

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"

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).

Read the 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.
Being tested
Clofarabine, Cyclophosphamide
Keywords
Adult patients, Refractory, Relapsed, clofarabine, cyclophosphamide, refractory and relapsed acute lymphoblastic leukemia, ALL
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Clofarabine, CyclophosphamideDrug

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

Study groups in NCT01462253
Study groupRoleWhat they receive
Clofarabine, CyclophosphamideExperimentalClofarabine 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.
Receives: Drug: Clofarabine, Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Primary End-point is the Number of Patients in CR After Induction Therapy.

    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.

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

Secondary outcomes (5)

  1. Number of Participants With Toxicity of Grade 2 or Greater

    Referring to CTCAE (Common Toxicity Criteria Events), version 4.0

    Measured: At 13 months from study entry

  2. Number of Participants With Minimal Residual Disease (MRD) Response in Remission.

    Measured: At week 10, 16 and 22 from start of treatment and the, every three months till study completion

  3. Disease-free Survival (DFS)

    Disease-free survival (DFS) at 1 year, defined as the time interval between the evaluation of CR and relapse of the disease or death in first CR; patients still alive, in first CR, will be censored at the time of the last follow-up. In this case, the DFS curve will be truncated at 1 year

    Measured: At one year from completion of chemotherapy

  4. Overall Survival (OS)

    Overall Survival (OS) at 1 year; defined as the time interval between inclusion and death for any cause; patients still alive will be censored at the time of the last follow-up. In this case, the OS curve will be truncated at 1 year.

    Measured: At one year from therapy completion.

  5. Cumulative Incidence of Relapse (CIR)

    Cumulative incidence of relapse (CIR) at 1 year, it will be calculated from the date of achievement of the first CR, using the cumulative incidence method, considering death in CR as a competing risk. Patients still alive, without a date of relapse, will be censored at the time of the last follow-up. In this case, the CIR curve will be truncated at 1 year.

    Measured: At one year from therapy completion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2011 (estimated)
  2. Study startOct 2012
  3. Primary completion11 Mar 2017
  4. Study completion11 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01462253
Sponsor's protocol ID
LAL1610
Acronym
LAL1610
Status last verified
Aug 2018
First submitted
21 Oct 2011
Last updated
25 Jan 2019
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clofarabine, Cyclophosphamide in people with Acute Lymphoblastic Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 27 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Primary End-point is the Number of Patients in CR After Induction Therapy. (time frame: At day +28 from start of chemotherapy cycle 1 and after cycle 2 in pts with PR). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01462253.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2019.

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