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

NCT01462253 | Completed Phase 2 Results

• 1 other identifier: LAL1610
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 27

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).

Conditions

Acute Lymphoblastic Leukemia

Keywords

Adult patients; Refractory; Relapsed; clofarabine; cyclophosphamide; refractory and relapsed acute lymphoblastic leukemia; ALL

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

• Number of Participants With Toxicity of Grade 2 or Greater

  At 13 months from study entry

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

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

• Disease-free Survival (DFS)

  At one year from completion of chemotherapy

• Overall Survival (OS)

  At one year from therapy completion.

• Cumulative Incidence of Relapse (CIR)

  At one year from therapy completion.

Study Arms (1)

Clofarabine, Cyclophosphamide

EXPERIMENTAL

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.

Drug: Clofarabine, Cyclophosphamide

Interventions

Clofarabine, Cyclophosphamide DRUG

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

Clofarabine, Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (27)

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, 70010, Italy

Location

Divisione di Ematologia - Ospedali Riuniti

Bergamo, Italy

Location

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

Bologna, Italy

Location

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

Bolzano, Italy

Location

Sezione di Ematologia e Trapianti Spedali Civili

Brescia, 21125, Italy

Location

Azienda ASL di Cagliari

Cagliari, 9121, Italy

Location

Ospedale Santa Croce Divisione di Ematologia Cuneo

Cuneo, Italy

Location

Policlinico di Careggi, Università delgi studi di Firenze

Florence, Italy

Location

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

Meldola, Italy

Location

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

Mestre, Italy

Location

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

Milan, Italy

Location

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, Italy

Location

Centro Oncologico Modenese - Dipartimento di Oncoematologia

Modena, Italy

Location

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

Monza, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, Italy

Location

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

Napoli, Italy

Location

Ospedale Cervello

Palermo, 90146, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, 65100, Italy

Location

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

Pisa, Italy

Location

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, Italy

Location

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

Reggio Calabria, Italy

Location

Umberto I di Roma - Dipartimento di Biotecnologie Cellulari ed Ematologia

Roma, 00161, Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

Roma, Italy

Location

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

Roma, Italy

Location

Università degli Studi - Policlinico di Tor Vergata

Roma, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

SCDO Ematologia 2 AOU Giovanni Battista

Torino, Italy

Location

Related Links

• GIMEMA Foundation Website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Clofarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Alfonso Piciocchi
• Organization: GIMEMA

a.piciocchi@gimema.it

+39 06 70390513

Study Officials

• Renato BASSAN, Pr.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2011
• First Posted: October 31, 2011
• Study Start: October 1, 2012
• Primary Completion: March 11, 2017
• Study Completion: March 11, 2017
• Last Updated: January 25, 2019
• Results First Posted: January 25, 2019

Record last verified: 2018-08

Locations

IT (27)