DOrianT: A Study to Investigate the Relationship Between Duration of Treatment and Response in Patients With Multiple Myeloma (MM) or Systemic AL Amyloidosis Treated in Real-life Practice

Sponsor

Takeda (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04659798

Collaborator

(none)

250

Enrollment

Locations

27.2

Anticipated Duration (Months)

17.9

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will provide information on outcomes in people with multiple myeloma, or systemic AL amyloidosis, or both, under standard care. AL is short for amyloid light-chain. Standard care means the participant will be treated according to their clinic's standard practice. The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study.

The aim of the study is to learn if treatment duration makes a difference in how participants with multiple myeloma or systemic AL amyloidosis respond to their treatment.

During the study, participants will be treated according to their clinic's standard practice. Participants must have started their treatment up to 12 months before taking part in this study. During the study, the participants will visit their clinic every 3 months. These are extra visits to their clinic's standard visits.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Immunoglobulin Light-chain Amyloidosis

Detailed Description

This is a prospective non-interventional study to assess the DoT and response in participants with MM or systemic AL amyloidosis in standard clinical practice.

This study will enroll approximately 250 participants (220 with MM and 30 with systemic AL amyloidosis). Participants will be enrolled in 2 groups:

Participants with MM Participants with AL amyloidosis The study will have a prospective data collection of the participants from clinical records and scheduled visits following the routine clinical practice. All participants will receive treatment at study start and this treatment must have been started within 12 months before the participant's enrollment.

This multi-center study will be conducted in Spain. Participants will be followed until 12 months after enrollment. The overall time to participate in this study is approximately 1 year.

Study Design

Study Type:

Observational

Anticipated Enrollment :

250 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prospective Non-interventional Study to Investigate the Relationship Between Duration of Treatment (DoT) and Response in Patients With Multiple Myeloma or Systemic AL Amyloidosis Treated in Real-life Clinical Practice

Actual Study Start Date :

Jan 22, 2021

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

Apr 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Participants with MM Participants diagnosed with MM who have received treatment within 12 months preceding the enrollment will be observed prospectively. Data will be collected from the participants medical charts and via electronic case report forms (eCRFs).
Participants with AL Amyloidosis Participants diagnosed with AL Amyloidosis who have received treatment within 12 months preceding the enrollment will be observed prospectively. Data will be collected from the participants medical charts and via eCRFs.

Outcome Measures

Primary Outcome Measures

DoT [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
DoT is defined as the time between the start of a treatment/regimen and the end of that regimen.
PFS [From date of the initiation of treatment or regimen the participant is receiving at the time of study entry until progression, death, or 1 year after end of treatment (approximately 1 year)]
PFS: time between start of treatment or regimen and progression or death. PFS for MM will be evaluated according to International Myeloma Working Group(IMWG) and defined per European Society for Medical Oncology(ESMO)guideline. Progressive disease(PD)for MM: increase of 25% from lowest confirmed response value in one of the following criteria: Serum M protein(absolute increase must be>=0.5 g/dL; Serum M protein increases >=1g/dL, if the lowest M component was 5g/dL; Urine M protein(absolute increase must be>=200 mg/24h).PFS for AL amyloidosis will be evaluated as per Guidelines of the British Society for Haematology(BSH).PD for AL amyloidosis: progression from complete response(CR)as any detectable M protein or abnormal free light chain(FLC) ratio(involved light chain must double).Progression from partial response(PR)is defined as a 50% increase in serum M protein to>5.0g/L or 50% increase in urine M protein to>200mg/dL(a visible peak must be present)or FLC increase of 50% to>100mg/L.

Secondary Outcome Measures

Time to Next Treatment (TTNT) [From start of current treatment or regimen until start of next treatment or regimen (approximately 1 year)]
TTNT is defined as time between start of current treatment or regimen and start of next treatment or regimen.
Number of Participants Categorized Based on Treatment Regimens Prescribed in Routine Clinical Practice [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Number of participants will be reported based on treatment regimens prescribed in routine clinical practice including the number of participants based on treatment line (example- first, second, third or fourth line of treatment), the type of regimen (fixed or continuous), the prescribed duration, and the drug combination used. Fixed duration therapy will be defined as regimen prescribed under a fixed number of cycles. Continuous therapy will be defined as a regimen planned to be administered for a prolonged time (example- 2-3 years), without a pre-defined number of cycles, until progression or intolerance of treatment.
Number of Participants Based on Treatment Response Achieved [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Treatment response as: CR,stringent CR(sCR),very good partial response(VGPR),PR, based on IMWG/ESMO guideline for MM; BSH for AL amyloidosis.For MM;CR:negative immunofixation on serum/urine,disappearance of any soft tissue plasmacytomas,<=5%PCs in BM, sCR:CR/normal FLC ratio,absence of clonal PCs by immunochemistry or 2-4 colour flow cytometry;VGPR:serum/urine M protein level <100 mg/24h,PR:reduction in serum M protein by >=50%and in 24h urinary M protein by >=90%or<200 mg/24h,>=50%decrease in difference between involved/uninvolved FLC levels required in place of M protein criteria, serum-free light assay is also unmeasurable,>= 50%reduction in PCs required in place of M protein provided baseline BM PC percentage was >=30%and >=50%reduction in size of soft tissue plasmacytomas if serum/urine M protein are unmeasurable. For AL amyloidosis;CR:normal FLC levels with normal kappa/lambda ratio, negative serum/urine immunofixations,VGPR:reduction in dFLC to <40 mg/l,PR:50%reduction in dFLC.
Number of Participants Categorized Based on Differences Between Prescribed and Actual DoT, and Reasons for Treatment Discontinuation [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Participants will be categorized on the basis of difference between prescribed and actual DoT by evaluating treatment duration and reason for treatment discontinuation.
Number of Participants Satisfied With the Treatment [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Participant satisfaction regarding treatment will be assessed using Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire V1.4. The TSQM questionnaire, Spanish version, is a generic measure of satisfaction with the prescribed medication consisting of 14 Likert response items of 7 or 5 alternatives, which assess independently: efficacy (3 items), adverse events (AE) (4 items), convenience of treatment (3 items) and overall satisfaction (3 items). Scores range from 0 to 100, with higher score indicates greater satisfaction in that domain.
Number of Participants Categorized Based on Clinical and Sociodemographic Characteristics Influencing the Treatment Prescribed and Satisfaction With Treatment [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Percentage of Participants With More Than one Neoplasm [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Percentage of Participants who Achieve the Prescribed DoT According to Treatment Strategy [From start date of treatment reported at study entry until discontinuation of treatment for any reason (approximately 1 year)]
Treatment strategy as fixed duration therapy or continuous therapy. Fixed duration therapy will be defined as regimen prescribed under a fixed number of cycles. Continuous therapy will be defined as a regimen planned to be administered for a prolonged time (example- 2-3 years), without a pre-defined number of cycles, until progression or intolerance of treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of MM and/or AL amyloidosis according to the IMWG for MM and BSH guidelines for AL amyloidosis.

MM diagnostic criteria:

Smouldering MM- Both criteria must be met:

Serum M protein (Immunoglobulin G [IgG] or IgA greater than or equal to (>=) 30 gram per liter (g/L) or urinary monoclonal protein (M protein) >= 500 milligram per 24 hours (mg/24 h) and/or clonal bone marrow (BM) plasma cells (PCs) 1 percent (%) - 60%.
Absence of myeloma-defining events or amyloidosis.

Multiple myeloma- Clonal BM plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma-defining events:

Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

Hypercalcemia: serum calcium greater than (>) 0.25 millimole per liter (mmol/L) (> 1 milligram per deciliter [mg/dL]) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
Renal insufficiency: creatinine clearance (CrCl) less than (<) 40 milliliter per minute (mL/min) or serum creatinine >177 micromole/liter (mcmol/L) (>2 mg/dL).
Anemia: haemoglobin (Hb) value of >20 g/L below the lower limit of normal or a Hb value of <100 g/L.
Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT) or positron emission tomography-computed tomography (PET-CT).

Any one or more of the following biomarkers of malignancy:

=60% clonal BM plasma cells.
Involved/uninvolved serum-free light chain ratio >=100.
1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be >=5 millimeter (mm) in size).

AL amyloidosis diagnosis:

In suspected AL amyloidosis, a histological diagnosis is essential and, where possible, a biopsy should be taken from an apparently affected organ. Alternatively, a subcutaneous abdominal fat aspirate and bone marrow biopsy may be examined for amyloid.
Congo red staining with classical apple green birefringence under polarized light should be used to test for the presence of amyloid on any histological specimen.
The diagnosis of amyloid requires an experienced laboratory as false negative and false positive diagnoses on the basis of histology are not infrequent. Other (non-AL) amyloid fibril types should be excluded by using immunohistochemistry, deoxyribonucleic acid (DNA) analysis, protein sequencing or mass spectrometry.

Under treatment for MM or systemic AL amyloidosis at the time of study entry.
Have started treatment up to 12 months before inclusion for MM or systemic AL amyloidosis, irrespective of the treatment regimen.
Having first, second, third or fourth line of treatment for MM or systemic AL amyloidosis, irrespective of the treatment regimen.
In case of participants with Newly Diagnosed Multiple Myeloma (NDMM) who are candidates to autologous stem cell transplant (ASCT), the ASCT has to be performed before study entry.

Exclusion Criteria:

Participants with planned cessation of treatment for MM or systemic AL amyloidosis from participation to the study (example, due to pregnancy).
Participating in blinded clinical trials, or in clinical trials with no possibility of obtaining information required in this study, or in clinical trials in which participation in other studies is not allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Puerta del Mar	Cadiz	Andalucia	Spain	11009
2	Hospital Regional Universitario de Malaga (Carlos de Haya)	Malaga	Andalucia	Spain	29010
3	H. Universitario de Cabuenes	Gijon	Asturias	Spain	33394
4	C.H.U. Canarias	La Laguna	Canarias	Spain	38320
5	H. Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
6	H. Universitario de Leon	Leon	Castilla Y Leon	Spain	24071
7	C.H. Salamanca	Salamanca	Castilla Y Leon	Spain	37007
8	H. Universitario Lucus Agusti	Lugo	Galicia	Spain	27003
9	C.H.U. Santiago	Santiago de Compostela	Galicia	Spain	15706
10	H. Universitari Son Espases	Palma de Mallorca	Islas Baleares	Spain	7120
11	Hospital General Universitario Santa Lucia	Cartagena	Murcia	Spain	30202
12	H. Universitario de Araba	Vitoria	Pais Vasco	Spain	1009
13	Hospital Universitario de Burgos	Burgos		Spain	9006
14	H. Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040