French Study to Highlight the Unmet Treatment Needs of 3L+ CP-CML and With T315I-mutated CML Patients

Chronic Myeloid Leukemia Clinical Trial

Official title:

A Multi-Center Retrospective Chart Review Study Examining the Patient Characteristics, Treatment Patterns, Clinical Outcomes, and Burden of Illness Among Patients With Chronic Myeloid Leukemia in Third-line Treatment or With T315I Mutation in France (CML 3L+ & T315I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05619978
• Other study ID #: CABL001A0FR01
• Status: Completed
• Start date: May 3, 2021
• Est. completion date: October 29, 2021

Study information

• Verified date: November 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A retrospective multi-center cohort study design was used to address the study objectives, using medical records obtained from three clinical centers in France.

Description:

The index date for patients in the 3L cohort was defined as the date of initiation of 3L therapy. The index date for the T315I cohort was defined as the date of treatment initiation with TKI or allogeneic stem cell transplantation (allo-SCT) after identification of T315I mutation status. The baseline (i.e., pre-index) period was defined as the 6 months prior to the index date, and the post-index period was defined as the time from the index date to the date of last patient contact or patient death. Patients who were alive at the end of the follow-up period were censored at the date of last contact.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 29, 2021
• Est. primary completion date: October 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Diagnosed with CML-CP

• Age =18 years at the time of CML-CP diagnosis

• For 3L patients: initiated one of the following 3L therapies in CML-CP after failing on =2 TKIs (i.e., bosutinib, dasatinib, imatinib, nilotinib, or ponatinib) or allo-SCT

• For T315I mutation patients: evidence of T315I mutation and treatment with TKI or allo-SCT

Exclusion Criteria:

• History of other active malignancies within the 3 years prior to the time of CML-CP diagnosis

• Documentation of anti-cancer therapies for any other malignancies prior to the time of 3L therapy initiation or at the time of treatment initiation after identification of T315I mutation

• Enrollment in a clinical trial at the time of 3L therapy initiation or at the time of treatment initiation after identification of T315I mutation

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Other:
• 3L Therapy
Treatments received in 3L were dasatinib, nilotinib, imatinib, ponatinib, bosutinib, and allo-SCT
• T315I
Patients with chronic myeloid leukemia with T315I mutation

Locations

Country	Name	City	State
France	Novartis Investigative Site	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients: Year patient initiated third-line treatment	Following categories included: Before 2010 2010-2014 2015-2019 2020-2021	throughout the study (study used data from 2000 to 2021)
Primary	Duration of third-line treatment	Duration of third-line treatment was reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients: Type of therapy received in third-line treatment	TKI agent; Allo-SCT	throughout the study (study used data from 2000 to 2021)
Primary	Time from 2L discontinuation to third-line treatment initiation	Time from 2L discontinuation to third-line treatment initiation was reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients still on 3L therapy as of data collection date	Number of patients still on 3L therapy as of data collection date was reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients discontinued 3L	Number of patients who discontinued 3L treatment were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients: Reasons for 3L discontinuation	Treatment switch due to AEs or intolerance; Treatment switch due to resistance; Treatment switch due to signs of ineffectiveness; Treatment switch due to other reasons	throughout the study (study used data from 2000 to 2021)
Primary	Number of lines of therapy for patients with chronic myeloid leukemia in third-line treatment	Number of lines of therapy for patients with chronic myeloid leukemia in third-line treatment were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of most frequent treatment sequences for patients with chronic myeloid leukemia in third-line treatment	Number of most frequent treatment sequences for patients with chronic myeloid leukemia in third-line treatment were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of last line of therapy for patients with chronic myeloid leukemia in third-line treatment	Number of last line of therapy for patients with chronic myeloid leukemia in third-line treatment were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients: Year patient initiated on the line identified as T315I line of interest	Following categories included: Before 2010 2010-2014 2015-2019	throughout the study (study used data from 2000 to 2021)
Primary	Duration of the line identified as T315I line of interest	Duration of the line identified as T315I line of interest was reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients: Type of therapy received in the line identified as T315I line of interest	TKI agent; Allo-SCT	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients still on line of therapy identified as T315I line of interest as of data collection date	Number of patients still on line of therapy identified as T315I line of interest as of data collection date were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of patients: Reasons for discontinuation on the line identified as T315I line of interest	Adverse events or intolerance; Resistance; Signs of ineffectiveness Suboptimal response Progression to accelerated phase or blast phase; Other reasons Acquired mutations	throughout the study (study used data from 2000 to 2021)
Primary	Number of lines of therapy for patients with chronic myeloid leukemia with T315I mutation	Number of lines of therapy for patients with chronic myeloid leukemia with T315I mutation were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of line identified as T315I line of interest	Number of line identified as T315I line of interest were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of treatment sequence for patients with chronic myeloid leukemia with T315I mutation	Number of treatment sequence for patients with chronic myeloid leukemia with T315I mutation were reported	throughout the study (study used data from 2000 to 2021)
Primary	Number of last line of therapy for patients with chronic myeloid leukemia with T315I mutation	Number of last line of therapy for patients with chronic myeloid leukemia with T315I mutation were reported	throughout the study (study used data from 2000 to 2021)
Secondary	Cytogenetic response (CyR) for 3L patients	CCyR, defined as an absence of Philadelphia chromosome-positive (Ph+) metaphases in bone marrow cytogenetics	12 and 24 months
Secondary	Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 12 months	Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 12 months were reported	12 months post treatment
Secondary	Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 24 months	Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 24 months were reported.	24 months post treatment
Secondary	Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 12 months	Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 12 months were reported.	12 months post treatment
Secondary	Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 24 months	Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 24 months were reported.	24 months post treatment
Secondary	Time to major molecular response (MMR) among patients with chronic myeloid leukemia in third-line treatment	Time to MMR was defined as the time from third-line (3L) treatment initiation to the time patients achieved MMR (i.e., 0.01% IS < BCR::ABL1 transcript level = 0.1% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to deep molecular response (MR4.0) among patients with chronic myeloid leukemia in third-line treatment	Time to MR4.0 was defined as the time from third-line (3L) treatment initiation to the time patients achieved MR4.0 (i.e., 0.0032% IS < BCR::ABL1 transcript level = 0.01% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to sustained deep molecular response (MR4.0) among patients with chronic myeloid leukemia in third-line treatment	Time to sustained MR4.0 was defined as the time from third-line (3L) treatment initiation to the time patients achieved sustained MR4.0 or better (i.e., BCR::ABL1 = 0.01%) in all consecutive assessments performed for at least 12 months (i.e., 365.25 days). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to deep molecular response (MR4.5) among patients with chronic myeloid leukemia in third-line treatment	Time to MR4.5 was defined as the time from third-line (3L) treatment initiation to the time patients achieved MR4.5 (i.e., 0.001% IS = BCR::ABL1 transcript level = 0.0032% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to sustained deep molecular response (MR4.5) among patients with chronic myeloid leukemia in third-line treatment	Time to sustained MR4.5 was defined as the time from third-line (3L) treatment initiation to the time patients achieved sustained MR4.5 or better (i.e., BCR::ABL1 = 0.0032%) in all consecutive assessments performed for at least 2 years (i.e., 730.5 days). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to Progression-free survival (PFS) for 3L patients	Time to PFS was defined as the time from third-line treatment initiation to earliest occurrence of documented disease progression to accelerated phase or blast crisis, or the date of death from any cause. Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, or end of data availability.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to Overall Survival (OS) for 3L patients	Time to OS was defined as the time from third-line treatment initiation to death from any cause. Patients were censored at the earliest of treatment discontinuation or switch, date of last follow-up, or end of data availability.	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Time to treatment discontinuation (TTD) for 3L patients	TTD was defined as the time from third-line treatment initiation to treatment discontinuation or switch. Patients were censored at the earliest of loss to follow-up, or end of data availability, or death	12, 24, 36, 48, 60, 72 and 84 months post treatment
Secondary	Proportion of patients with Adverse Events (AEs) in third-line treatment	Proportion of patients with Adverse Events (AEs) were reported to evaluate the safety profile of third-line treatments for chronic myeloid leukemia	throughout the study (study used data from 2000 to 2021)
Secondary	Age of patients with chronic myeloid leukemia in third-line treatment	Age information was reported.	Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021)
Secondary	Number of patients: Year of chronic myeloid leukemia in chronic phase (CML-CP) diagnosis of patients with chronic myeloid leukemia in third-line treatment	Year of CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment was reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Sex of patients with chronic myeloid leukemia in third-line treatment	Sex information was reported.	Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021)
Secondary	Number of patients: Medical center of patients with chronic myeloid leukemia in third-line treatment	The following centers were included: Centre Léon Bérard, Lyon Hématologie Institut Bergonié, Bordeaux Institut Universitaire du Cancer Toulouse, Toulouse	Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021)
Secondary	Length of follow-up (month) characteristics of patients with chronic myeloid leukemia in third-line treatment	Length of follow-up was defined as time from index date to the date of last known contact with patient or patient death.	throughout the study (study used data from 2000 to 2021)
Secondary	Number of patients: Smoking status at index date of patients with chronic myeloid leukemia in third-line treatment	Smoking status at index date of patients with chronic myeloid leukemia in third-line treatment was reported.	Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021)
Secondary	Time from CML-CP diagnosis to index date (month) of patients with chronic myeloid leukemia in third-line treatment	Time from CML-CP diagnosis to index date (month) of patients with chronic myeloid leukemia in third-line treatment was reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Number of patients with Hasford score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment	Low risk (=780) Intermediate risk (>780 to =1480) High risk (>1480) Not assessed Unknown / not sure	throughout the study (study used data from 2000 to 2021)
Secondary	Number of patients with Sokal score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment	Low risk (<0.8) Intermediate risk (=0.8 to =1.2) High risk (>1.2) Not assessed Unknown / not sure	throughout the study (data source from 2000 to 2021)
Secondary	Number of patients with ELTS risk score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment	ELTS: EUTOS long-term survival Low risk (=1.5680) Intermediate risk (>1.5680 to =2.2185) High risk (>2.2185) Not assessed Unknown / not sure	throughout the study (data source from 2000 to 2021)
Secondary	Number of patients with BCR::ABL1 rearrangement at CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment	Major Minor Other	throughout the study (data source from 2000 to 2021)
Secondary	Number of patients with Additional chromosomal abnormalities at CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment	Yes No	throughout the study (study used data from 2000 to 2021)
Secondary	Number of comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment	Number of comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment were reported.	Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy)
Secondary	Number of patients with comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment	Cardiovascular disease Pulmonary disease/pulmonary arterial hypertension Gastrointestinal issues Renal disease Diabetes Liver disease Other No comorbidities Unknown / not sure	Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy)
Secondary	Number of patients with any ischemic condition prior to the index date in patients with chronic myeloid leukemia in third-line treatment	Cardiovascular disease Cerebrovascular disease Peripheral arterial	Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy)
Secondary	Number of patients with Cardiovascular risk factors prior to the index date in patients with chronic myeloid leukemia in third-line treatment	Hypertension Hyperlipidemia/dyslipidemia Diabetes Obesity	Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy)
Secondary	Laboratory and clinical results: Random blood glucose (mg/dl)	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Fasting blood glucose (mg/dl)	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: LDL cholesterol (mg/dl)	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Total cholesterol (mg/dl)	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Blood pressure	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Spleen size below costal margin	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Blood cell count	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Laboratory and clinical results: Bone marrow differential cell count	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Number of patients with BCR::ABL1 mutation status by line of therapy for patients with chronic myeloid leukemia in third-line treatment	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)
Secondary	Proportion of patients achieving response among patients with chronic myeloid leukemia with T315I mutation	Laboratory and clinical results were reported.	throughout the study (study used data from 2000 to 2021)