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EUCTR2013-002076-41

Study to determine whether ixazomib citrate (MLN9708) as maintenance therapy has an effect on progression free survival and overall survival compared to placebo in patients with newly diagnosed multiple myeloma who have received induction therapy followed by high-dose therapy and autologous stem-cell transplantation

Datenbasis: WHO (Import vom 09.12.2018)
Geändert: 04.11.2018
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Newly diagnosed multiple myeloma (NDMM) following induction therapy and autologous stem cell transplant (ASCT)
MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864

Interventions (Datenquelle: WHO)


Product Name: ixazomib capsules (MLN9708) 0.5 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: NINLARO
Product Name: ixazomib capsule (MLN9708) 2.3 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: NINLARO
Product Name: ixazomib capsule (MLN9708) 3.0 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: NINLARO
Product Name: ixazomib capsule (MLN9708) 4.0 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
1. Adult male or female patients 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.
2. Documented results available for cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant and for ISS staging at the time of diagnosis.
3. Underwent standard of care induction therapy (induction therapy must include PI and/or IMiD-based regimens as primary therapy for multiple myeloma), followed by a single ASCT with a high-dose melphalan (200 mg/m2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin (doxorubicin), and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
4. Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant.
5. Patient must have not received post-ASCT consolidation therapy.
6. Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
7. ECOG performance status of 0 to 2.
8. Female patients who:
* If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, AND
* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Male patients, even if surgically sterilized (ie, status postvasectomy), who:
* Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND
* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
9. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
10. Suitable venous access for the study-required blood sampling.
11. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
12. Patients must meet the following clinical laboratory criteria at study entry:
* Absolute neutrophil count (ANC) = 1,000/mm3 and platelet count = 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before randomization.
* Total bilirubin = 1.5 x the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
* 3 = ULN.
* Calculated creatinine clearance = 30 mL/min.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion criteria:
1. Multiple myeloma which has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.
2. Double (tandem) ASCT.
3. Radiotherapy within 14 days before the first dose of study drug.
4. Diagnosed or treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy with evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
5. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
6. Major surgery within 14 days before randomization.
7. Central nervous system involvement.
8. Infection requiring IV antibiotic therapy or other serious infection within 14 days before randomization.
9. Diagnosis of Waldenstrom’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
11. Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort within 14 days before randomization in the study.
12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, PN that is Grade 1 with pain or Grade 2 or higher of any cause).
14. Psychiatric illness/social situation that would limit compliance with study requirements.
15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
17. Treatment with any investigational products within 60 days before the first dose of the study drug regimen.

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002076-41

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2013-002076-41

Weitere Informationen zur Studie

Registrationsdatum der Studie

29.04.2014

Einschluss der ersten teilnehmenden Person

14.07.2014

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 2

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: To determine the effect of ixazomib maintenance therapy on PFS, compared to placebo, in patients with NDMM who have had a response (CR, very good partial response [VGPR], or partial response [PR]) to induction therapy followed by HDT and ASCT;Secondary Objective: * Determine the effect of ixazomib maintenance therapy on OS compared to placebo;Primary end point(s): Progression-free survival (PFS), defined as the time from the date of randomization to the date of first documentation of disease progression, as evaluated by an independent review committee (IRC) using IMWG
(International Myeloma Working Group) criteria, or death due to any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Baseline up to End of treatment (24 months)

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): Overall survival (OS), measured as the time from the date of randomization to the date of death

Kontakt für Auskünfte (Datenquelle: WHO)

Millennium Pharmaceuticals, Inc.

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Mexico, Netherlands, Norway, Poland, Portugal, Republic of, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Drug Information Call Center
40 Landsdowne Street
Millennium Pharmaceuticals, Inc.
15107402412
medical@mlnm.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Drug Information Call Center
40 Landsdowne Street
Millennium Pharmaceuticals, Inc.
15107402412
medical@mlnm.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Millennium Pharmaceuticals, Inc.

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

C16019;NCT02181413