PASCA-MM Study. Impact of the PASCA (PArcours de Santé au Cours du CAncer) Program on Complications Associated With Multiple Myeloma and/or Its Treatments in the Context of a First Hematopoietic Stem Cell Autograft, in Adults Aged 18 to 70. (PASCA -MM)

This is a prospective, multicentre, phase III, randomised, controlled intervention study.

Two groups of patients with equal numbers will be studied and each patient will be allocated to one of the two groups described below by randomisation (ratio 1:1).

Each patient will be allocated to one of the two groups described below by randomisation (ratio 1:1).

- PASCA interventional group

For both the 7 complications of interest (primary objective) and the 13 secondary complications (secondary objective), a specific and proactive referral will be made systematically after each screening assessment, depending on the level of risk, estimated according to decision trees (management guide) and through the dedicated PASCA network of healthcare professionals, in order to initiate early treatment and follow-up if necessary.

- Control group

For the 7 complications of interest (primary objective) as well as for the 13 complications (secondary objective): all the data from each identification check-up will be sent to the onco-haematological transmitted to the referring onco-haematologists, so that they can initiate their own management.

=> For all patients, regardless of group

All patients will receive four screening assessments covering the 7 complications of interest and 13 secondary complications:

• Visit No.1 (T1), 1-2 months after the autologous haematopoietic stem cell transplantation (aHSCT), corresponding to the patient's visit to his or her Multiple Myeloma (MM) monitoring consultation and/or the start of his or her consolidation treatment.
• Visit No.2 (T2), 4 months after aHSCT, corresponding to a patient's visit for the end of consolidation treatment;
• Visit No.3 (T3), 14 months after the last aHSCT, corresponding to a visit by the patient during his or her maintenance treatment;
• Visit No.4 (T4), 24 months after the last aHSCT, corresponding to a visit by the patient for a MM monitoring consultation.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Complication
• Intervention / Treatment: Behavioral: Interpretation of the results from the detection visit; Behavioral: Explaining detection results and referrals to the patient; Behavioral: Early medical care through the network; Behavioral: Transmission of results from each detection visit to the referring onco-haematologists - Control Group

Detailed Description

After each screening visit, all patients randomised to the intervention group will receive the PASCA intervention:

1. An interpretation of the results of the screening tests concerning

   • the 7 complications of interest assessed at T1, T2, T3 and T4 ;
   • the 13 secondary complications assessed at T1, T3 and T4. This interpretation will be based on decision trees (1 tree/complication) to guide investigators in their decision-making and to standardise orientations;
2. Explanation of results and referrals to the patient using plain language, by a phone call, ;
3. Early, proactive care via a dedicated network of healthcare professionals.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Romain BUONO, PharmaD, MPH; Phone Number: +33469856358; Email: romain.buono@lyon.unicancer.fr
• Study Contact Backup: Name: Meyssane DJEBALI, Msc; Phone Number: ++33426556743; Email: meyssane.djebali@lyon.unicancer.fr

Study Locations

• France
  • Lyon, France, 69373
    • Recruiting
    • Centre LEON BERARD
    • Sub-Investigator: Amine BELHABRI
    • Sub-Investigator: Anne-Sophie MICHALLET
    • Sub-Investigator: Philippe REY
    • Contact: Mauricette MICHALLET, MD; Phone Number: +3346998566358; Email: mauricette.michallet@lyon.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 70 years old.
2. Patient treated in an investigation center.
3. Symptomatic multiple myeloma eligible for autologous hematopoietic stem cell transplantation (HSCT).
4. In stringent complete response, complete response, very good complete response, or partial before HSCT.
5. First induction-type treatment (Isa-KRD/dara-VRD/dara-VTD/VRD/VTD), intensification therapy with melphalan, HSCT, consolidation, maintenance including at least one drug immunomodulator.
6. ECOG performance status WHO ≤ 2.
7. No history or coexistence of other primary cancer apart from basal cell cancer cutaneous
8. Able to understand, read and write French.
9. Having signed and dated the informed consent.

Exclusion Criteria:

1. Unable to be monitored for medical, social, family, geographical or psychological, throughout the duration of the study.
2. Deprived of liberty by court or administrative decision.
3. Not affiliated with a health insurance plan.
4. Not having declared an attending physician.
5. Not domiciled in the Auvergne-Rhône-Alpes region or in the Saône-et-Loire department.
6. Not available and/or not willing to participate in the project for the entire duration of the study.
7. Pregnant women, breastfeeding women, people in emergency situations, people incapable of personally giving their consent including adults under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; For both the 7 complications of interest (primary objective) and the 13 secondary complications (secondary objective), specific and proactive referrals will be made systematically after each detection visit according to the level of risk, estimated on the basis of decision trees (management guide) and via the dedicated PASCA network of healthcare professionals, to initiate early treatment and follow-up where necessary.	Behavioral: Interpretation of the results from the detection visit; - An interpretation of the results of the detection tests concerning; the 7 complications of interest assessed at T1, T2, T3 and T4 ;; the 13 secondary complications assessed at T1, T3 and T4. This interpretation will be based on decision trees (1 tree/complication) to guide investigators in their decision-making and to standardise orientations; Behavioral: Explaining detection results and referrals to the patient; Explanation of results and directions to the patient using plain language;The aims of this call are as follows: Clearly explain the results of the detection visit and the action to be taken for each referral;; Evaluate the help to be given to the patient. This help will consist of making bookings with a healthcare professional in the PASCA network;; Reassure patients about their results, but also make them aware of the importance of taking action to improve or prevent the onset of complications.; Behavioral: Early medical care through the network; Early, proactive medical care through a network of dedicated healthcare professionals.
Active Comparator: Control group; For both the 7 complications of interest (primary objective) and the 13 secondary complications (secondary objective): all the data from each detection visit will be sent to the referring forwarded to the referring onco-haematologists, so that they can initiate their own management.	Behavioral: Transmission of results from each detection visit to the referring onco-haematologists - Control Group; For both the 7 complications of interest (primary objective) and the 13 secondary complications (secondary objective): all the data from each detection visit will be sent to the referring onco-haematologists, so that they can initiate their own management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from Baseline high blood pressure	blood pressure ≥ 140/90 mmHg measured in the investigating center and persisting over time	month 2, month 4, month 14 and month 24
Change from Baseline chronic kidney failure incidence at 24 months	diagnosed on the basis of 2 blood tests carried out within 3 months with the same technique showing either: a decrease in GFR to < 60ml/min/1.73m2, estimated from serum creatinine using the CKD-EPI equation (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009),; positive proteinuria or albuminuria (albuminuria/creatinine ratio),; haematuria with a GR > 10/mm3 or 10,000/ml (after eliminating a urological cause),; leucocyturia with a WBC >10/mm3 or 10,000/ml (in the absence of infection),; a morphological abnormality on renal ultrasound: size asymmetry, bumpy contours, small kidneys or large polycystic kidneys, nephrocalcinosis, cyst. The evolutionary character corresponds to one of the following situations: Annual decline in GFR ≥ 5 ml/min/1.73 m²/year: GFR year n - GFR year n+1; Presence of albuminuria,; Poorly controlled arterial hypertension	month 2, month 4, month 14 and month 24
Change from Baseline chronic pain incidence at 60 months	pain felt for more than 3 months by the patient with an intensity on the Visual Analogue Scale (VAS) ≥ 3	month 2, month 4, month 14 and month 24
Change from Baseline sexual disorders incidence at 24 months	at least one perceived problem among the following: disorders of desire,; arousal/erection disorders in men,; arousal disorders (insufficiency) in women,; Orgasm disorders in women	month 2, month 4, month 14 and month 24
Change from Baseline osteoporosis incidence at 24 months	T-score evaluated by osteodensitometry, on the lumbar spine and upper end of the femur	month 2, month 14 and month 24
Change from Baseline chronic fatigue incidence at 24 months	Questionnaire "MFI-20" (Multidimensional Fatigue Inventory)	month 2, month 4, month 14 and month 24
Change from Baseline severe anxiety disorder incidence at 24 months	Questionnaire "HADS-D" (Hospital Anxiety and Depression scale)	month 2, month 4, month 14 and month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline depressive events incidence at 24 months	Defined by at least two main depressive symptoms, associated with at least two symptoms additional information, according to the 2017 HAS recommendation "Characterized depressive episode in adults : care in first resort".	month 2, month 4, month 14 and month 24
Change from Baseline physical deconditioning incidence at 24 months	Defined by at least two tests among the 6 min Walk Test (TDM6), Handgrip-test, 60s Sit-to-stand, Flamingo test, with usual values below the norms defined by their authors, according to age and sex	month 2, month 14 and month 24
Change from Baseline cognitive problems incidence at 24 months	Positive score on at least one of the sub-dimensions of the Functional questionnaire Cancer Therapy Assessment - Cognitive Function (FACT-COG)	month 2, month 14 and month 24
Change from Baseline hypogonadism incidence at 24 months	Presence of clinical signs as defined by the International Society for Sexual Medicine A value below the lower limit on at least one of the following blood assay: level of total testosterone; level of bioavailable testosterone	month 2, month 14 and month 24
Change from Baseline obesity incidence at 24 months	BMI value: [25-30[ kg/m2 with a waist circumference above the norm (≥ 94cm for men or≥ 80cm for women); ≥ 30 kg/m2	month 2, month 14 and month 24
Change from Baseline hypothyroidism incidence at 24 months	level of thyroid-stimulating hormone; level of total thyroxine	month 2, month 14 and month 24
Change from Baseline dyslipidemias incidence at 24 months	hypercholesterolemia (LDL) ≥ 1.6 g/L estimated by the Friedewald formula and/or a hypertriglyceridemia ≥ 4 g/L	month 2, month 14 and month 24
Change from Baseline Heart failure markers incidence at 24 months	NT-proBNP and/or troponin I level above the threshold values.	month 2, month 14 and month 24
Change from Baseline Atrial fibrillation incidence at 24 months	equivocal electrocardiogram, interpreted by an experienced physician	month 2, month 14 and month 24
Change from Baseline of respiratory failure markers incidence at 24 months	FVC, FVC, FEV1, FEF25-75, FEF50, FEF25 (established by spirometric test) ≤ 80% of the predicted values (abacus on age, sex, height and origin ethnic)	month 2, month 14 and month 24
Change from Baseline return to work issues incidence at 24 months	Diagnosed by a social worker	month 2, month 14 and month 24
Change from Baseline of Lifestyle risk factors ( tobacco, alcohol, and cannabis) incidence at 24 months	consumption : smoking and/or active cannabis; alcohols higher than the latest recommendations	month 2, month 4, month 14 and month 24
Change from baseline Myelodysplastic syndromes and secondary acute leukemia incidence at 24 months	confirmed by the reference diagnosis	month 4, month 14 and month 24

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Collaborators: National Cancer Institute, France
• Investigators: Principal Investigator: Mauricette MICHALLET, PhD, MD, Centre LEON BERARD

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): September 14, 2027

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 7, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Detection; Multiple Myeloma; Complications; Intervention; Randomized controlled trials; Autologous stem cell transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: PASCA-MM (ET22000285)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No