Advancing Chemical and Genomic Strategies for Relapsed/Refractory T-ALL and ETP-ALL

NCT ID: NCT04582487

Last Updated: 2024-02-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-19

Study Completion Date

2024-05-31

Brief Summary

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This is a biological study for R/R T-ALL/LBL or ETP-ALL patients. Bone marrow and/or peripheral blood samples will be subjected to genomic, DSRP profiling and phosphoproteomic screening to identify novel potential therapeutic approach and thus, eligibility for treatment based on molecular and DSRP data. As soon as genomic and DSRP profiling are made available, local Investigator can submit to local ethic committee a request for clinical use of identified compound.

Detailed Description

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This is a biological study for R/R T-ALL/LBL or ETP-ALL patients. Bone marrow and/or peripheral blood samples will be subjected to genomic, DSRP profiling and phosphoproteomic screening to identify novel potential therapeutic approach and thus, eligibility for treatment based on molecular and DSRP data.

Genomic studies include karyotyping, CI-FISH and sequencing of 72 selected genes recurrently involved in T-ALL (by NGS).

A panel of 80 compounds has been choosen for DSRP profile.

As soon as genomic and DSRP profiling are made available, local Investigator can submit to local ethic committee a request for clinical use of compound hits. Meanwhile, in case of leukocytosis and uncontrolled disease, patients will be treated with cytoreductive therapies and best supportive care according to guidelines and scientific consensus.

Every patient will receive a molecularly and functionally informed therapy following the therapeutic schedule already defined by in other tumors. Treatment will be selected on the basis of integration of genomic and small response data.

Conditions

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T Acute Lymphoblastic Leukemia Early T Acute Lymphoblastic Leukemia T-lymphoblastic Lymphoma Etp All

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Biological evaluation

A combined approach of Drug Sensitivity and Resistance Profiling (DSRP) and molecular-cytogenetic findings is used in order to prioritize compounds for tailored therapies.

Group Type OTHER

bone marrow and/or peripheral blood samples withdrawal

Intervention Type OTHER

bone marrow and/or peripheral blood samples evaluation

Interventions

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bone marrow and/or peripheral blood samples withdrawal

bone marrow and/or peripheral blood samples evaluation

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients to be enrolled in this study must have T-cell ALL or T-cell lymphoblastic lymphoma (LL) in the first relapse or must have failed primary induction chemotherapy (i.e., never attained a complete remission following an initial course of standard therapy for T-ALL/LBL or have a diagnosis of ETP-ALL \[T-ALL with the following phenotype: Negative: CD1a-, CD8-, CD4-, CD5 (less than 75% of blasts); CD13+, CD33+, CD34+, CD117+, HLA-DR+, CD11b+, and/or CD65+ -in at least 25% of lymphoblasts
* Ages Eligible for Study: over 18 years
* Patients with T-ALL/LBL must have greater than 5% blasts in the bone marrow with or without extramedullary disease
* Patients with T-ALL/LBL must have recurrent disease, documented by clinical or radiographic criteria, as well as histologic verification of the malignancy at original diagnosis
* Patients may have CNS 1 (WBC count in CSF \<5 and having no blasts) or CNS 2 (WBC count in CSF \<5 and having blasts) disease but not CNS 3 (WBC count in CSF ≥5 and having blasts)
* ECOG 0-2 or Karnofsky ≥ 50%
* Patients may be enrolled on study regardless of the timing of prior Intrathecal therapy; however, they may not begin treatment on this protocol until a minimum of 7 days has elapsed since prior intrathecal therapy
* Adequate renal function defined as serum creatinine ≤ 1.5x upper limit of normal (ULN) for age. If the serum creatinine is above these values, the calculated creatinine clearance or radioisotope GFR must be ≥ 70 mL/min/1.73m2
* Total bilirubin ≤ 1.5x ULN for age. If the total bilirubin is elevated, patient will still be eligible if the conjugated (direct) serum bilirubin ≤ ULN for age
* ALT ≤ 5x ULN of normal for age
* Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 45% by gated radionuclide study
* No evidence of dyspnea at rest
* No exercise intolerance
* A pulse oximetry ≥ 94% at sea level (≥ 90% at altitude ≥ 5000 feet) if there is clinical indication for determination
* Patients must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients must sign a written informed consent

Exclusion Criteria

* Significant organ compromise that will increase risk of toxicity or mortality
* Active serious infection not controlled by oral or intravenous antibiotics
* Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
* Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
* Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
* Patients with a cardiac ejection fraction (as measured by either multigated acquisition \[MUGA\] or echocardiogram) \< 40%
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica

Ancona, , Italy

Site Status RECRUITING

Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia

Bergamo, , Italy

Site Status RECRUITING

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

Bologna, , Italy

Site Status RECRUITING

Asst Degli Spedali Civili Di Brescia - Uo Ematologia

Brescia, , Italy

Site Status RECRUITING

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

Lecce, , Italy

Site Status RECRUITING

Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

Mestre, , Italy

Site Status RECRUITING

Ematologia ed Immunologia Clinica

Perugia, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica

Roma, , Italy

Site Status RECRUITING

Aou Senese - Uoc Ematologia E Trapianti

Siena, , Italy

Site Status RECRUITING

Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia

Vicenza, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Paola Fazi

Role: CONTACT

0670390528

Enrico Crea

Role: CONTACT

0670390514

Facility Contacts

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Attilio Olivieri

Role: primary

3289558821

Alessandro Rambaldi

Role: primary

3484526901

Cristina Papayannidis

Role: primary

3496484441

Erika Borlenghi

Role: primary

3402526539

Nicola Di Renzo

Role: primary

3388178577

Renato Bassan

Role: primary

Cristina Mecucci

Role: primary

Roberta La Starza

Role: backup

Simona Sica

Role: primary

3355952379

Monica Bocchia

Role: primary

3495792804

Albana Lico

Role: primary

Other Identifiers

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ALL2720

Identifier Type: -

Identifier Source: org_study_id

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