Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 (1) with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study.

Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study.

Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR.

Carmen Fava, MD, PhD

Giulia Piraccini, MA

The investigator propose an extension of the previous National, multicentric study, promoting an observational registry, both retrospective and prospective, in order to expand and further characterize the series of Italian patients with Philadelphia-positive, chronic phase CML (CP-CML) who discontinue TKIs in an off-protocol setting. As safety concerns may arise for patients receiving long-term treatments, and due to the growing number of patients discontinuing TKIs in clinical practice, the study aim to collect all available data regarding feasibility and freedom from progression of the cohort of patients.

This is an observational, retrospective and prospective study of CP-CML patients who discontinue TKIs in Italy. The study will not imply additional costs for the participating centers. Data already present in the clinical charts will be collected.

The patients, answering to inclusion/exclusion criteria will be enrolled in one of the follow cohorts

* Cohort 1 retrospective/prospective study: 293 patients enrolled and reported in Fava et al 2019 with at least 1 year of follow up at the end of the study (February 2017) and 107 patients enrolled but not reported in Fava et al 2019 since their follow-up was shorter than 1 year. The data for these patients will be collected since the end of previous study.
* Cohort 2 retrospective/prospective study: patient not enrolled in the previous study (Fava et al 2019). The data for these patients will be collected since patient diagnosis to the end of the study.
* Cohort 3 prospective study: patients who have discontinued TKI therapy after the study approval in each center. These patients will also participate in the validation process of Phase 2 of a questionnaire developed by an expert panel of eight CML patients with the purpose of capturing the experiences of people along all phases of the TFR.

Patients participating in the study will not be subjected to any procedure that falls outside the clinical practice; in the same way, clinical variables that will be collected for the study are those that are commonly collected by physician in daily clinical practice.

Any decision about drug administration or suspension is made by the physician based on his clinical judgment in the context of clinical practice, independently from decision to include the patient in this study.

Registration of enrolled patients will be done on-line on a key restricted accessible web-database.

Primary objective and endpoint To assess the TFR rate at 1 year from discontinuation of TKIs. Secondary objectives and endpoints

* To further describe the observed population of patients in terms of:

  * treatment-free duration; o survival in MR4.5;
  * survival in MR3;
  * event-free survival;
  * progression-free survival;
  * deaths after treatment discontinuation;
  * rate of achievement of MMR and DMR after treatment re-initiation
* To identify clinical and biological prognostic factors affecting the persistence of off-therapy remission.
* To identify optimal timing and modalities of molecular monitoring of BCR-ABL1 transcript

  * Evaluation of the safe minimum monitoring during and after treatment discontinuation
  * Evaluation of the maximum MRD positivity level acceptable to safely stay off-treatment
* Evaluation of short-term adverse events (withdrawal syndrome: fever, arthralgia, myalgia, bone pain, weight loss) after treatment discontinuation
* Evaluation of long-term adverse events (i.e. cardiovascular adverse events, second neoplasia) after treatment discontinuation
* Validation of the Italian version of the "Phase 2" of a questionnaire developed by an expert panel of eight CML patients to capture the experiences of people along all phases of the TFR
* Evaluation of patient-reported outcomes describing quality of life of patients off therapy and after resumption of TKIs

Italian Treatment Free Remission Registry

Observational Study in Adult Patient With Chronic Myeloid Leukemia Who Discontinue Tyrosine Kinase Inhibitors in Italy

To assess the TFR rate at 1 year from discontinuation of TKIs

treatment-free duration (months); survival in MR4.5 (%); survival in MR3 (%); event-free survival (%); progression-free survival (%); deaths after treatment discontinuation (%); rate of achievement of MMR and DMR after treatment re-initiation (%)

University of Turin, Italy

Antineoplastic Agents

Tin Fluorides

Imatinib Mesylate

Fluorides

Protective Agents

Patients of CML who remain in sustained molecular remission at 12 months after Stopping the standard drug therapy

Stopping the standard drug therapy of CML patients and monitoring their treatment free remission status

Stopping the standard drug therpy

Monthly recording of quantitative bcrabl by RQPCR on patients peripheral blood derived RNA. RQPCR will have minimum sensitivity of log4.5

Quantitative bcrabl recording every month for first 6 months

Patients with chronic myeloid leukemia (CML) are conventionally put on life long therapy with tyrosine kinase inhibitor drugs (Imatinib mesylate in India). Patients who achieve a deep molecular response which has been sustained for at least three years, can be taken off the drug therapy. Thereafter a close monitoring is required to monitor their disease relapse. In case there is evidence of disease recurrence on highly sensitive molecular assays, their drug therapy is restarted. The study aims to identify proportion of patients who can be kept off drug therapy in a state of sustained molecular remission.

While a large number of studies which have stopped TKI therapy in similar patients exist in Europe and USA, no such study has been done on Indian or other south Asian population. Almost all studies done previously have noted that in relapsed patients, who show disease recurrence on stopping their TKI therapy, their remission state is regained once the TKI therapy is restarted.

To Study the Impact of Stopping Therapy in Patients of CML With Molecular Remission

Stopping Imatinib Therapy in CML Patients With Sustained Molecular Remission

Re-appearance of bcr-abl transcripts by RQPCR at a level \>0.01%

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Italian Treatment Free Remission Registry	NCT04769947	Treatment Free ... Chronic Myeloid...		18 Years -	University of Turin, Italy
To Study the Impact of Stopping Therapy in Patients of CML With Molecular Remission	NCT03062436	Chronic Myeloid... Treatment Free ...	Stopping the st... Quantitative bc...	12 Years - 75 Years	Command Hospital, India
To Study the Impact of Stopping Therapy in Patients of CML With Molecular Remission	NCT03062436	Chronic Myeloid... Treatment Free ...	Stopping the st... Quantitative bc...	12 Years - 75 Years	Command Hospital, India

Spots Global Cancer Trial Database for treatment free remission