Study to determine whether adding MLN9708 to the combination of cyclophosphamide and dexamethasone improves the response to therapy in patients who have been newly diagnosed with multiple myeloma and have not received previous anti-myeloma treatment

Phase 1

• Conditions: ewly diagnosed multiple myeloma; MedDRA version: 14.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003113-17-GR
• Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-04
• Last Update Posted: 10 October 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Adult male or female patients 18 years of age or older with a confirmed diagnosis of symptomatic MM according to standard criteria (see Section 14.1 and Section 14.5) who have not received prior treatment for MM.
2. Patients for whom cyclophosphamide and dexamethasone treatment is appropriate and who are considered not eligible for HDT-SCT for 1 or more of the following reasons:
* The patient is 65 years of age or older.
* The patient is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.
3. Patients must have measurable disease defined by at least 1 of the following
3 measurements:
* Serum M-protein = 1 g/dL (= 10 g/L).
* Urine M-protein = 200 mg/24 hours.
* Serum free light chain assay: involved free light chain level = 10 mg/dL (= 100 mg/L), provided that the serum free light chain ratio is abnormal.
4. Patients must meet the following clinical laboratory criteria:
* Absolute neutrophil count (ANC) = 1000/mm3 and platelet count = 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to study drug dosing.
* Total bilirubin = 1.5 x the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
= 3 x ULN.
* Calculated creatinine clearance (CrCL) = 30 mL/min (see Section 14.2).
5. Eastern Cooperative Oncology Group performance status of 0, 1, or 2 (see Section 14.3).
6. Female patients who:
* Are postmenopausal for at least 1 year before the screening visit, or
Are surgically sterile, or
* 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, 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, 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.)
7. 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.
8. Suitable venous access for the study-required blood sampling.
9. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
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 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen. (NOTE: Prior treatment with corticosteroids (maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone over 14 days. Localized radiation is permitted as long as it is below a therapeutic level and administered at least 14 days prior to the first dose of study treatment.)
2. Diagnosis of smoldering MM, Waldenström’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
3. Central nervous system involvement.
4. Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any 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. Peripheral neuropathy Grade 1 with pain or = Grade 2 of any cause on clinical examination during the Screening period.
6. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
7. Infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
8. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection
9. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort within 14 days before the first dose of study treatment.
10. Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
11. Major surgery within 14 days before the first dose of study drug. (NOTE: Kyphoplasty or vertebroplasty is not considered major surgery.)
12. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
13. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
14. 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.
15. Treatment with any investigational products for reasons other than MM within 30 days before the first dose of study drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified