STUDY THAT COMPARE 3 ARM: MLN9708 DEXAMETHASONE, MLN9708 CYCLOPHOSPHAMIDE AND DEXAMETHASONE, MLN9708 THALIDOMIDE AND DEXAMETHASONE FOLLOWED BY MAINTENANCE WITH MLN9708 IN NEWLY DIAGNOSED ELDERLY MULTIPLE MYELOMA PATIENTS

NCT02586038 | Completed Phase 2

• 1 other identifier: UNITO-EMN10
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and the efficacy of the MLN-DEXAMETHASONE, MLN-DEXAMETHASONE-CYCLOPHOSPHAMIDE, or MLN- THALIDOMIDE-DEXAMETHASONE induction combinations, followed by MLN maintenance in newly diagnosed elderly Multiple Myeloma patients. 183 patients, males and females, older than 65 years old or younger but considered not eligible for high-dose chemotherapy and transplantation, enrolled in different sites, will take part in this study. The duration of the study is approximately 5 years.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Number of patients that will experience a progression disease after 2 years from diagnosis in 3 induction treatments, followed by maintenance with MLN9708, including: * MLN9708 plus dexamethasone (MLN-DEX) * MLN9708 plus dexamethasone and cyclophosphamide (MLN-CYCLO-DEX) * MLN9708 plus dexamethasone and thalidomide (MLN-THAL-DEX) A maximum of 61 patients per arm will be evaluated.

  2 years

Secondary Outcomes (6)

• Response rate

  5 years

• Toxicity in terms of rate of hematologic and non-hematologic adverse events

  5 years

• Progression Free Survival-2 (PFS-2)

  5 years

• Time To Progression (TTP)

  5 years

• Time to Next Therapy (TNT)

  5 years

Study Arms (2)

MLN-DEX-CYCLO arm

EXPERIMENTAL

Patients will receive nine 28-days induction cycles. MLN9708: 4,0 mg orally on days 1, 8, 15 Dexamethasone: 40 mg orally on days 1, 8, 15, 22. Cyclophosphamide: 300 mg/sqm orally on days 1, 8, 15

Drug: MLN9708; Drug: Dexamethasone; Drug: Cyclophosphamide

MLN-DEX-THAL arm

EXPERIMENTAL

Patients will receive nine 28-days induction cycles. MLN9708: 4,0 mg orally on days 1, 8, 15 Dexamethasone: 40 mg orally on days 1, 8, 15, 22. Thalidomide: 100 mg/day orally

Drug: MLN9708; Drug: Dexamethasone; Drug: Thalidomide

Interventions

MLN9708 DRUG

MLN-DEX-CYCLO arm; MLN-DEX-THAL arm

Dexamethasone DRUG

MLN-DEX-CYCLO arm; MLN-DEX-THAL arm

Cyclophosphamide DRUG

MLN-DEX-CYCLO arm

Thalidomide DRUG

MLN-DEX-THAL arm

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Female patient is either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
• Newly diagnosed MM based on standard CRAB criteria (see Appendix 12.2).
• Age ≥ 65 years old or younger not eligible for transplantation.
• Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein (M-protein) value (, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• Clinical laboratory values within 30 days of enrolment:
• platelet count ≥ 75 x 109/L (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment)
• haemoglobin ≥ 8 g/dL
• absolute neutrophil count (ANC) ≥ 1.0 x109/L
• AST and ALT ≤ 3 times the upper limit of normal
• total bilirubin ≤ 1.5 times the upper limit of normal
• clearance creatinine ≥ 30 ml/min

You may not qualify if:

• Pregnant or lactating females.
• Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk.
• Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid \< to the equivalent of dexamethasone 40 mg/day for 4 days)
• Clinical active infectious hepatitis type A, B, C or HIV (HBV-DNA and HCV-RNA will be analysed to evaluate the cell proliferation of virus; anti-HIV antibody must be negative).
• Acute active infection requiring antibiotics or infiltrative pulmonary disease
• Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.03
• Contraindication to any of the required drugs or supportive treatments
• Invasive malignancy within the past 3 years
• Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort within 14 days before the first dose of study treatment (see Appendix 12.12).
• Diagnosis of Waldenstrom's macroglobulinemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
• 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.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.

Sponsors & Collaborators

• Mario Boccadoro: lead

Study Sites (1)

AO SS Antonio e Biagio e Cesare Arrigo di Alessandria

Alessandria, 15121, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Dexamethasone; Cyclophosphamide; Thalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 26, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

IT (1)