A Phase 1/ 2 Study of the Oral Form of MLN9708 with Melphalan and Prednisone for Patients with Newly Diagnosed Multiple Myeloma
- Conditions
- ewly diagnosed multiple myelomaMedDRA version: 17.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-023772-71-GB
- Lead Sponsor
- Millennium Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 61
1. Male or female patient for whom standard MP treatment is indicated and who is not a candidate for HDT-SCT for 1 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 likely to have a negative impact on tolerability of HDT-SCT.
2. Symptomatic MM or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria
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 within 3 days before the first dose of study treatment to be enrolled in the study:
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 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 = 30 mL/min
5. ECOG performance status of 0 to 2
6. 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 line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
7. 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
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Agree to practice true abstinence when this is line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
8. 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2
1. Peripheral neuropathy = Grade 2 on clinical examination during the screening period.
2. Female patients who are lactating or pregnant.
3. Major surgery within 14 days before the first dose of study drug. (Note: kyphoplasty or vertebroplasty is not considered major surgery.)
4. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
5. Diarrhea >Grade 1, based on the NCI CTCAE grading, in the absence of antidiarrheals.
6. Prior systemic therapy for MM, including investigational drugs. Prior treatment with corticosteroids or localized radiation therapy does not disqualify the patient (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone, a total of which can be given in a 2-week period.
7. Radiotherapy within 14 days before the first dose of study treatment.
8. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), 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.
9. Central nervous system involvement.
10. 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.
11. 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.
12. QTc > 470 msec on a 12-lead ECG obtained during the Screening period. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG.
13. Known or suspected human immunodeficiency virus (HIV) positive.
14. Known or suspected hepatitis B surface antigen-positive status or known or suspected active hepatitis C infection.
15. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
16. Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
17. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
18. 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 a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method