Cyclophosphamide, Carfilzomib, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Active Multiple Myeloma
- Conditions
- Multiple MyelomaStage III Multiple MyelomaStage II Multiple MyelomaStage I Multiple Myeloma
- Interventions
- Registration Number
- NCT01057225
- Lead Sponsor
- Mayo Clinic
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I cyclophosphamide 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. Arm I carfilzomib 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. Arm I thalidomide 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. Arm I dexamethasone 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.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (Phase I) 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 DLTsPercentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II) 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 Outcome Measures
Name Time Method Progression-free Survival (Phase II) From baseline to progression or death up to 3 years PFS was defined as the time from registration to progression or death due to any cause. Progression was defined as any one or more of the following:
• Increase of 25% from lowest confirmed response in: Serum M-component (absolute increase must be ≥ 0.5 g/dl)c Urine M-component (absolute increase must be ≥ 200 mg/24 hour) If at on study, only the measurable non-bone marrow parameter was FLC, the difference between involved and uninvolved FLC levels (absolute increase must be \>10 mg/dl) Bone marrow plasma cell percentage (absolute % must be 10%)d Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
• Development of hypercalcemia (corrected serum calcium \>11.5 mg/dl) that can be attributed solely to the plasma cell proliferative disorderTime to Treatment Failure From baseline to end of active treatment The time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they were removed from treatment. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier
Stem Cell Collection and Engraftment (Phase II) Following the first 4 courses of treatment For patients going on to stem cell collection, the total number of CD34 positive cells collected per collection, days to platelets over 20,000 without transfusion and ANC over 1000 will be recorded. If a patient fails to collect adequate stem cells for transplant, this will be recorded as such. The number of patients with successful stem cell mobilization are reported.
Complete Response (Phase II) Following the first 4 courses of treatment In patients continuing beyond 4 cycles the ability to induce complete response will be evaluated at completion of planned therapy.
Survival Time (Phase II) From baseline to death Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier
Progression Free Survival (12 Month) 12 months Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. This is reported as the percentage of patients alive and progression free at the 12 month mark.
Progession Free Survival (24 Month) 24 months Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. This is reported as the percentage of patients alive and progression free at the 24 month mark.
Overall Survival (12 Month) From baseline to death 12 Month Overall survival is defined as the proportion of patients to still be alive after 12 months.
Overall Survival (24 Month) From baseline to death 24 Month Overall survival is defined as the proportion of patients to still be alive after 24 months.
Trial Locations
- Locations (3)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States