A Phase I/II Trial of Cyclophosphamide, Carfilzomib, Thalidomide and Dexamethasone (CYCLONE) in Patients With Newly Diagnosed Active Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- carfilzomib
- Conditions
- Multiple Myeloma
- Sponsor
- Mayo Clinic
- Enrollment
- 64
- Locations
- 3
- Primary Endpoint
- Maximum Tolerated Dose (Phase I)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.
Detailed Description
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. (Phase I) II. In newly diagnosed myeloma to evaluate the response rate (CR, nCR, and VGPR) to carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone after four 28 day cycles. (Phase II) SECONDARY OBJECTIVES: I. Determine the overall response rate (CR, nCR, PR) after 4, 8, 12 cycles. II. Determine the duration of progression-free and overall survival for patients receiving this regimen. III. To evaluate the incidence of toxicities for this regimen. IV. To evaluate the ability to successfully collect peripheral blood stem cells following four months of combination therapy. OUTLINE: This is a phase I, dose escalation study of carfilzomib followed by a phase II study. Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3 months, then every 3 months for 1 year, and then every 6 months for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
Intervention: carfilzomib
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
Intervention: cyclophosphamide
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
Intervention: thalidomide
Arm I
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
Intervention: dexamethasone
Outcomes
Primary Outcomes
Maximum Tolerated Dose (Phase I)
Time Frame: From baseline to end of active treatment, up to 12 28-day cycles.
To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, possibly) in the first or second cycle for patients enrolled to Dose Levels -1 and 0 and in the first cycle only for patients enrolled to Dose Levels 1 and 2. We are reporting the number of DLTs
Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II)
Time Frame: Following the first 4 cycles of treatment (28 day cycles)
The proportion of patients who have at least a confirmed very good partial response will be calculated by taking the number of patients with a very good partial response or a complete response divided by the total number of patients. A complete response is defined as: * Negative immunofixation of the serum and urine * If at on study, only the measurable non-bone marrow parameter was FLC, normalization of FLC ratio * \< 5% plasma cells in bone marrow * Disappearance of any soft tissue plasmacytomas A very good partial response is defined as: * Serum and urine M-component detectable by immunofixation but not on electrophoresis or * If at on study, serum measurable, ≥ 90% or greater reduction in serum Mcomponent * Urine M-component \<100 mg per 24 hour
Secondary Outcomes
- Progression-free Survival (Phase II)(From baseline to progression or death up to 3 years)
- Time to Treatment Failure(From baseline to end of active treatment)
- Stem Cell Collection and Engraftment (Phase II)(Following the first 4 courses of treatment)
- Complete Response (Phase II)(Following the first 4 courses of treatment)
- Survival Time (Phase II)(From baseline to death)
- Progression Free Survival (12 Month)(12 months)
- Progession Free Survival (24 Month)(24 months)
- Overall Survival (12 Month)(From baseline to death)
- Overall Survival (24 Month)(From baseline to death)