Phase 3 Randomized, Open-Label Clinical Trial of Tanespimycin (KOS-953) plus Bortezomib Compared to Bortezomib Alone in Patients with Multiple Myeloma in First Relapse
- Conditions
- Patients with multiple myeloma in first relapse after failure of previous anti-cancer therapy and/or bone marrow transplantationMedDRA version: 9.1Level: LLTClassification code 10028228Term: Multiple myeloma
- Registration Number
- EUCTR2007-004138-17-AT
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 466
1. Age = 18 years
2. KPS performance status = 70%
3. All patients must have documented evidence of multiple myeloma. All patients must have documented progression of disease after initial response to one line of therapy (either relapse from CR or progressive disease by EBMT/IBMTR criteria; see Section 5.3.1). Patients who proceeded to high-dose chemotherapy followed by stem cell transplantation (autologous or allogeneic; myeloablative or non-myeloablative; single or tandem) without documented progressive disease prior to SCT remain eligible for this protocol. Patients who received maintenance therapy following the SCT also remain eligible for this protocol, provided progression by EBMT/IBMTR criteria was not observed between SCT and initiation of maintenance
therapy. If the patient begins a second antimyeloma agent (for example, dexamethasone) without documented prior progression on the single-agent therapy, this will count as one regimen
4. All patients must have measurable disease (serum M-protein > 0.5 g/dL or > 200 mg urinary M-protein excretion/24-hour). (Patients who meet these criteria for measurable disease must also meet requirement for documentation of progressive disease by EBMT criteria). Patients with non-secretory or oligosecretory
disease are not eligible for the study. Disease must be assessed within 14 days prior to randomization
5. For those patients who received prior bortezomib or a bortezomib-containing regimen: patients must have achieved a CR or PR by EBMT/IBMTR criteria. Patients may not have received a bortezomib-containing regimen following SCT as
maintenance therapy
6. All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade = 2 (except for neuropathy and diarrhea which must be Grade = 1 and painful neuropathy which must have resolved)
7. The following laboratory results, within 14 days of randomization:
Hemoglobin = 7.5 g/dL (if transfused within 14 days of randomization, pre- transfusion hemoglobin = 7 g/dL)
Absolute neutrophils count = 0.750 x 10 to the 9/L (with or without growth factor support within 14 days of randomization)
Platelet count = 50 x 10 to the 9/L (without platelet transfusions within 14 days prior to randomization; if transfused within 14 days of randomization, pre-transfusion platelet count must be = 50 x 10 to the 9/L)
Total bilirubin = 2 x ULN
AST = 2.5 x ULN
Serum creatinine = 2 x ULN or = 20 mL/min CrCL
Pregnancy test (serum or urine): negative (in all women of child-bearing potential)
8. Signed informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use a physical method of contraception or agree to complete sexual abstinence throughout her participation on trial. Female patients with childbearing potential must have a negative pregnancy test within 14 days prior to randomization. Male patients must be surgically sterile or agree to use an acceptable method of contraception, including abstinence
2. Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 21 days prior to randomization (14 days for non-myelosuppressive therapy in which drug-related toxicities have resolved per
Inclusion Criterion #6). Patients should be 6 weeks from last dose of nitrosourea or monoclonal antibody, 10 weeks from autologous SCT, and 16 weeks from allogeneic SCT
3. For patients who have received prior allogeneic SCT: patients with moderate-to-severe chronic graft versus host disease (GvHD) as defined in Filipovich et al 2005
4. Treatment with plasmapheresis within 30 days prior to randomization
5. Prior therapy with a heat shock protein 90 inhibitor or an investigational proteasome inhibitor
6. Concurrent use of corticosteroids other than low dose oral prednisone of 5 mg qd or less (or its equivalent); inhaled corticosteroids for the treatment of pulmonary disease that result in little-to-no systemic absorption are permitted. Patients
currently receiving corticosteroids at a higher dose must have corticosteroids safely tapered to this level at least 7 days prior to randomization to be eligible
7. Grade 3 dyspnea (dyspnea with activities of daily living) or a requirement for supplemental oxygen
8. Known or suspected cardiac amyloidosis; POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes), or plasma cell leukemia (defined as either 20% of peripheral WBC
comprised of CD138+ cells or an absolute count of 2 x 10 to the 9 /L)
9. Known hepatitis A, B or C viral infection; HIV infection
10. Any medical conditions that, in the Investigator’s opinion, would impose excessive risk to the patient. Examples of such conditions include congestive heart failure of Class III or IV of the NYHA classification, infection requiring parenteral antiinfective treatment, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent
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