Study to evaluate the effectiveness of a combination of 3 treatments, followed by transplantation of their own blood cell progenitor cells for patients under 70 years of age with asymptomatic multiple myeloma at high risk of developing into symptomatic myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion PETHEMA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Jun 2015 → ongoing

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516908-42-00

EudraCT number

2014-002948-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the rate of patients in immunophenotypic response [i.e., complete response (CR) with minimal residual disease (MRD)-negative status using multiparametric flow cytometry (MFC) on day +100 after high-dose therapy followed by peripheral blood stem cell transplantation (HDT-ASCT or High-dose therapy / autologous stem cell transplant

Secondary objectives 6

1. • Evaluate the rate of patients in immunophenotypic response (i.e., CR with MRD-negative status, by mutliparametric flow cytometry) after consolidation and at 3 and 5 years post-transplant
2. • Evaluate efficacy in terms of response: sCR, CR, VGPR and PR after the different phases of treatment: induction, transplantation, consolidation, and maintenance.
3. • Evaluate TTP to symptomatic disease.
4. • Evaluate PFS.
5. • Evaluate OS.
6. • Evaluate the safety profile during the different phases of the study: induction, high-dose melphalan followed by autologous transplantation, consolidation, and maintenance.

Conditions and MedDRA coding

Smoldering multiple myeloma with high risk of progression to symptomatic myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. • The patient must, in the investigator’s opinion, be able to fulfill all of the clinical trial requirements.
2. • The patient must voluntarily sign the informed consent document before any study procedures that are not part of standard clinical care are carried out. The patient must be made aware that they can withdraw from the study at any time without this affecting their future medical care.
3. • The patient must be aged between 18 and 70 years, and eligible to receive high-dose therapy and autologous peripheral blood stem cell transplant.
4. • The patient must have been diagnosed with SMM with high risk of progression to symptomatic MM, or ultra-high risk of progression to symptomatic disease in the five years prior to inclusion in the study. It should be emphasized that we are referring to a diagnosis of high-risk SMM during this time period, not to monoclonal gammopathy, or intermediate or low-risk smoldering myeloma. In other words: o SMM with high risk of progression to symptomatic disease: 1. ≥ 10% BM clonal PC and presence of a monoclonal protein, IgG >3 g/dl or IgA >2 g/dl or Bence Jones proteinuria of >1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine < 2 mg/dl) and anemia (hemoglobin > 10 g/dl, or not 2 g/dl below the lower limit of normal.) 2. ≥ 10% BM clonal PC or IgG >3 g/dl or IgA >2 g/dl, or Bence Jones proteinuria > 1 g/24 h (but not both at the same time), always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients can be included in the study if they fulfill the following additional criteria: - Presence of a percentage of phenotypically abnormal PC in the in plasma cell compartment of the BM (aPC/PC) ≥ 95% and immunoparesis, defined as a reduction in the concentration of 1 or 2 immunoglobulins (lgs) by more the 25%, compared with the normal values of the corresponding lg. o SMM with ultra-high risk of progression to symptomatic disease: 1. Appearance of more than 1 focal lesion on MRI (ideally whole-body MRI) 2. Clonal PC in BM ≥ 60%. 3. Ratio of involved /uninvolved sFLC greater than 100 together with involved free light chain levels great than 100 mg/L.
5. • The patient must present an ECOG performance status of < 2.
6. • The patient must be able to attend scheduled visits.
7. • Women with gestational capacity must have a negative pregnancy test (serum or urine) which will be taken in the 14 days prior to initiation of treatment with the study drug. Sexually active women must also agree to use two methods of contraception [hormonal contraceptives (oral, injectable, or implants)], tubal ligation, intrauterine device, barrier methods with spermicide, or her partner has had a vasectomy) while receiving the study drug. Women with gestational capacity must agree to have a pregnancy test every 4 weeks (urine or serum) while receiving the study drug (or every 14 days if they have irregular menstrual cycles), and 4 weeks after receiving the last dose of the study drug.

Exclusion criteria 17

1. • Any physical or mental health condition that prevents the patient from signing or understanding the informed consent document.
2. • The patient has received prior treatment for SMM.
3. • The patient is pregnant or breastfeeding.
4. • The patient has lytic lesions, anemia, renal failure or hypercalcemia.
5. • Any of the following abnormal laboratory values: o Absolute neutrophil count (ANC) < 1,000/mm3. o Platelet count < 75,000/mm3. o Serum GOT or GPT > 3 times the upper limit of normal. o Total serum bilirubin > 2 times the upper limit of normal.
6. • History of neoplasms other than multiple myeloma (except in the case of basal cell skin cancers, squamous cell cancers or carcinoma in situ of the cervix or breast unless the patient has been disease-free for >5 years.
7. • The patient has undergone major surgery in the 4 weeks prior to inclusion in the study.
8. • The patient has active HIV, hepatitis B or hepatitis C infection.
9. • The patient has received an investigational drug of any type in the 4 weeks prior to inclusion in the study.
10. • The patient has experienced unstable angina or myocardial infarction in the 6 months prior to recruitment, class III or IV cardiac failure (according to the New York Heart Association criteria) uncontrolled angina, a history of acute coronary artery syndrome, uncontrolled ventricular arrhythmias, sick sinus syndrome or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities, unless the patient has a pacemaker.
11. • Uncontrolled hypertension or diabetes.
12. • Significant neuropathy (grades 3-4, or grade 2 with pain), in the 14 days prior to recruitment.
13. • Known history of allergies to captisol (a derivative of cyclodextrin that is used to dissolve carfilzomib).
14. • The patient presents a contraindication that prevents the administration of the concomitant or adjunctive treatments, including hydration intolerance due to pre-existing pulmonary or cardiac impairment.
15. • LVEF < 40
16. • Pulmonary hypertension.
17. • Presence of an acute active infection that requires treatment (systemic antibiotics, antivirals, or antifungal agents), in the 14 days prior to recruitment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Immunophenotypic complete remission (CR by flow cytometry) day +100 after induction treatment and HDT-ASCT.

Secondary endpoints 4

1. • Immunophenotypic complete remission (CR by flow cytometry), after consolidation and maintenance, and at 3 and 5 years post-HDT-ASCT.
2. • Response rates (sCR, CR, VGPR and ORR) after the different phases of treatment (induction, HDT-ASCT, consolidation, maintenance and rescue therapy).
3. • TTP to symptomatic disease, PFS and OS.
4. • Safety profile after the different phases of treatment: induction, high-dose melphalan treatment and autologous hematopoietic stem cell transplantation, consolidation, maintenance and rescue therapy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion PETHEMA

Sponsor organisation

Fundacion PETHEMA

Address

Oficinas 3 4 5, Calle De Santa Balbina 2 Calle De Santa Balbina 2

City

Madrid

Postcode

28023

Country

Spain

Scientific contact point

Organisation

Fundacion PETHEMA

Contact name

Juan José Lahuerta

Public contact point

Organisation

Fundacion PETHEMA

Contact name

Juan José Lahuerta

Third parties 6

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications