Observational Study of Conception/Pregnancy in Adult Patients With CML Treated With Tyrosine Kinase Inhibitors

NCT ID: NCT01752062

Last Updated: 2022-01-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 148 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-05-02
• Study Completion Date: 2022-12-31

Brief Summary

The objective of this study is to acquire more information about what we are doing during pregnancy in CML patients, in order to possibly establish in the future a consensus on the management of patients receiving TKIs who wants to father a child or become/are pregnant.

Detailed Description

The management of patients with chronic myeloid leukemia (CML) during pregnancy is a matter of continued debate. The introduction of the TKIs in clinical practice has dramatically changed the prognosis of CML. Patients diagnosed in chronic phase can reasonably expect many years of excellent disease control and good quality of life. Thus, the need to address issues related to fertility and pregnancy have arisen. Physicians are frequently being asked for advice regarding the need for, and or the appropriateness of, stopping treatment in order to conceive. The management of fertility begins at diagnosis. This means that immediate and future treatments should be considered at the very beginning. Therefore, the maintenance of fertility should be taken into account since diagnosis. Imatinib is not genotoxic but might lead to a decrease in sperm counts. Nevertheless, Imatinib is teratogenic in rats when given during organogenesis at doses higher than 100 mg/kg, approximately equivalent to 800 mg/day in men. Until now, approximately 60 pregnancies were reported in partners of men on Imatinib. No suggestions of any problems in conception, pregnancy, delivery or any increase in congenital abnormalities were reported. Regarding women, 204 patients were exposed to Imatinib, and 180 were reported in literature (76, 77). Of 180 women exposed to imatinib during pregnancy, outcome data are available for 125 (69%). Of those with known outcomes, 50% delivered normal infants and 28% underwent elective terminations, 3 following the identification of abnormalities. There were a total of 12 infants in whom abnormalities were identified, 3 of which had strikingly similar complex malformations that are clearly a cause for concern. It appears that although most pregnancies exposed to imatinib are likely to have a successful outcome, there remains a risk that exposure may result in serious fetal malformations. Although numbers are small there has been a disturbing cluster of rare congenital malformations such that imatinib cannot be safely recommended, particularly during the period of organogenesis. Last but not least, it has recently been reported a poor outcome after reintroduction of Imatinib in patients who interrupt therapy for pregnancy without having achieved an optimal response (78), introducing another variable in the management of women pregnant while receiving Imatinib. Only few data are available about the use of second generation TKIs, Nilotinib and Dasatinib, during pregnancy. Dasatinib is not mutagenic in rats (in vitro and in vivo tests), but is clastogenic in CHO cells. It does not seem to have such effect on fertility of male and female rats. However, it gives skeletal alterations in rats and rabbits and has embryolethality in rats if administered during pregnancies. Eleven pregnancies were reported while in dasatinib: 5 patients delivered normal infants, while 3 elective termination and 2 spontaneous abortion were reported. On the other hand, 9 male patient conceived during dasatinib: 8 normal infants were delivered, and 1 case was ongoing at the time of the report. Nilotinib is not mutagenic in rats. It does not have any effect on fertility in male and female rats. When administered during pregnancy, there is no evidence of teratogenicity but it is embryo and foetotoxic in the rat and in the rabbit. Only sporadic cases of patients who had been pregnant/had conceived during Nilotinib have been reported, and no speculation should be made from these data. In summary, there are virtually no data regarding II generation TKIs, that must be discontinued by women wishing to become pregnant. Several questions still remains unanswered regarding the management of patients receiving TKIs who want to conceive, or who have been exposed to TKI during pregnancy/conception.

Conditions

Chronic Myeloid Leukemia; Pregnancy

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Age > 18 years;
• Ph+/BCR-ABL+ CML in any phase of disease;
• Conception/pregnancy while diagnosed with CML
• Treatment with TKIs (before or after pregnancy);
• Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion Criteria

• Patient < 18 years
• Patients that suffer from any condition or illness that could prevent the patient to participate

• Minimum Eligible Age: 18 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

Elisabetta Abruzzese

Role: PRINCIPAL_INVESTIGATOR

Hematology, S. Eugenio Hospital, Rome

Locations

Unità Operativa di Oncologia - Presidio Ospedaliero N. Giannetasio - Azienda ASL 3 Rossano (CS)

Rossano, Cosenza, Italy

Site Status: NOT_YET_RECRUITING

Azienda Ospedaliera - Nuovo Ospedale "Torrette"

Ancona, , Italy

Site Status: RECRUITING

S.G. Moscati Hospital

Avellino, , Italy

Site Status: NOT_YET_RECRUITING

UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

Bari, , Italy

Site Status: RECRUITING

Divisione di Ematologia - Ospedali Riuniti Bergamo

Bergamo, , Italy

Site Status: RECRUITING

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

Bologna, , Italy

Site Status: RECRUITING

Spedali Civili - Azienda Ospedaliera - U.O. Ematologia

Brescia, , Italy

Site Status: RECRUITING

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

Site Status: RECRUITING

ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO

Cagliari, , Italy

Site Status: RECRUITING

Unità di Onco-Ematologia - Azienda Ospedaliera - Garibaldi

Catania, , Italy

Site Status: RECRUITING

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, , Italy

Site Status: RECRUITING

Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna

Ferrara, , Italy

Site Status: NOT_YET_RECRUITING

Policlinico di Careggi, Università Degli Studi Firenze

Florence, , Italy

Site Status: RECRUITING

Clinica Ematologica - DiMI - Università degli Studi di Genova

Genova, , Italy

Site Status: RECRUITING

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, , Italy

Site Status: RECRUITING

Ospedale Niguarda "Ca Granda"

Milan, , Italy

Site Status: RECRUITING

UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: RECRUITING

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

Monza, , Italy

Site Status: RECRUITING

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" Napoli

Napoli, , Italy

Site Status: RECRUITING

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

Napoli, , Italy

Site Status: RECRUITING

Ospedale San Gennaro - ASL Napoli 1

Napoli, , Italy

Site Status: RECRUITING

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Site Status: RECRUITING

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2 Prof. Giuseppe Saglio

Orbassano, , Italy

Site Status: RECRUITING

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"

Palermo, , Italy

Site Status: RECRUITING

Ospedale La Maddalena - Palermo

Palermo, , Italy

Site Status: NOT_YET_RECRUITING

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

Site Status: RECRUITING

Div. di Ematologia IRCCS Policlinico S. Matteo

Pavia, , Italy

Site Status: RECRUITING

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, , Italy

Site Status: NOT_YET_RECRUITING

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Site Status: RECRUITING

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

Piacenza, , Italy

Site Status: RECRUITING

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

Pisa, , Italy

Site Status: RECRUITING

Ematologia - Ospedale San Carlo

Potenza, , Italy

Site Status: RECRUITING

Ospedale S. M. delle Croci

Ravenna, , Italy

Site Status: RECRUITING

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

Reggio Calabria, , Italy

Site Status: RECRUITING

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Site Status: RECRUITING

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia

Roma, , Italy

Site Status: RECRUITING

Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo

Roma, , Italy

Site Status: RECRUITING

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena- I.F.O. Istituto Nazionale Tumori Regina Elena Roma

Roma, , Italy

Site Status: RECRUITING

U.O.C. Ematologia - Ospedale S.Eugenio

Roma, , Italy

Site Status: RECRUITING

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Site Status: RECRUITING

UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"

Roma, , Italy

Site Status: RECRUITING

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Site Status: RECRUITING

Ematologia - Dipartimento di Medicina Clinica e Sperimentale

Sassari, , Italy

Site Status: RECRUITING

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

Site Status: RECRUITING

U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati

Taranto, , Italy

Site Status: NOT_YET_RECRUITING

Azienda ospedaliera S. Maria di Terni

Terni, , Italy

Site Status: NOT_YET_RECRUITING

SCDO Ematologia 2 AOU S. Giovanni Battista

Torino, , Italy

Site Status: RECRUITING

Sezione di Ematologia - Med.II Div. Presidio Ospedaliero S. Chiara di Trento

Trento, , Italy

Site Status: NOT_YET_RECRUITING

Azienda U.L.S.S.9 - U.O. di Ematologia

Treviso, , Italy

Site Status: RECRUITING

Policlinico Universitario - Clinica Ematologia

Udine, , Italy

Site Status: RECRUITING

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, , Italy

Site Status: NOT_YET_RECRUITING

ULSS N.6 Osp. S. Bortolo

Vicenza, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Paola Fazi, Dr.

Role: CONTACT

p.fazi@gimema.it

Enrico Crea

Role: CONTACT

e.crea@gimema.it

Facility Contacts

Francesco Iuliano, Dr.

Role: primary

Anna Rita Scortechini, Dr.

Role: primary

Fausto Palmieri, Dr.

Role: primary

Giorgina Specchia

Role: primary

Alessandro Rambaldi, Dr.

Role: primary

Fausto Castagnetti, Dr.

Role: primary

Mariadele Capucci, Dr.

Role: primary

Angela Melpignano, Dr.

Role: primary

Emilio Usala, Dr.

Role: primary

Ugo Consoli, Dr.

Role: primary

Fabio Stagno, Dr.

Role: primary

Antonio Cuneo, Dr.

Role: primary

Alberto Bosi, Dr.

Role: primary

Ivana Pierri, Dr.

Role: primary

Caterina Musolino, Dr.

Role: primary

Ester Pungolino, Dr.

Role: primary

Alessandra Iurlo, Dr.

Role: primary

Carlo Gambacorti Passerini, Dr.

Role: primary

Felicetto Ferrara, Dr.

Role: primary

Fabrizio Pane, Dr.

Role: primary

Lucia Mastrullo, Dr.

Role: primary

Gianluca Gaidano, Dr.

Role: primary

Giovanna Rege, Dr.

Role: primary

Clementina Caracciolo, Dr.

Role: primary

Maurizio Musso, Dr.

Role: primary

Diamante Turri, Dr.

Role: primary

Ester Orlandi, Dr.

Role: primary

Giuseppe Visani

Role: primary

Roberto Di Lorenzo, Dr.

Role: primary

Elena Trabacchi, Dr.

Role: primary

Sara Galimberti, Dr.

Role: primary

Michele Pizzuti, Pr.

Role: primary

Marzia Salvucci, Dr.

Role: primary

Francesco Nobile, Dr.

Role: primary

Paolo Avanzini, Dr.

Role: primary

Enrico Montefusco, Dr.

Role: primary

Leonardo Pacilli, Dr.

Role: primary

Atelda Dr. Romano

Role: primary

Elisabetta Abruzzese, Dr.

Role: primary

Simona Sica

Role: primary

Giuliana Alimena, Dr.

Role: primary

Nicola Cascavilla, Dr.

Role: primary

Claudio Fozza

Role: primary

Monica Bocchia, Dr.

Role: primary

Alessandro Maggi, Dr.

Role: primary

Anna Maria Liberati, Dr.

Role: primary

Patrizia Pregno, Dr.

Role: primary

Paolo Vivaldi, Dr.

Role: primary

Filippo Gherlinzoni, Dr.

Role: primary

Mario Tiribelli, Dr

Role: primary

Massimiliano Bonifacio, Dr.

Role: primary

Anna D'Emilio, Dr.

Role: primary

Related Links

http://www.gimema.it

GIMEMA Foundation

Other Identifiers

CML1012

Identifier Type: -

Identifier Source: org_study_id