Multiple Myeloma Clinical Trial
Official title:
A Phase I/II Trial of Cyclophosphamide, Carfilzomib, Thalidomide and Dexamethasone (CYCLONE) in Patients With Newly Diagnosed Active Multiple Myeloma
Verified date | November 2017 |
Source | Mayo Clinic |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 64 |
Est. completion date | September 5, 2017 |
Est. primary completion date | March 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion - Creatinine =< 2 mg/dL - Calculated Creatinine Clearance >= 30 mL/min - Total Bilirubin =< 2.0 mg/dL - Alkaline Phosphatase =< 3 x ULN - ALT =< 3 x ULN - Absolute neutrophil count >= 1000/uL - Platelet >= 75000/uL - Hemoglobin >= 8.0 g/dL - Untreated symptomatic myeloma: Prior non-systemic therapy for the treatment of solitary plasmacytoma is permitted, but >= 1 month should have elapsed from the last day of radiation; prior therapy with clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the Principal Investigator - Prior high dose corticosteroid therapy for twelve days (480 mg total dose) or less is permitted for emergent complications from newly diagnosed multiple myeloma - Measurable disease of multiple myeloma, as defined by at least ONE of the following: - Serum monoclonal protein >= 1.0 g by protein electrophoresis - OR > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis - OR serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; OR monoclonal bone marrow plasmacytosis >= 30% (evaluable disease) - ECOG performance status (PS) 0, 1, 2; ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator - Willingness and able to provide informed written consent - Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only - Willingness to return to Mayo Clinic enrolling institution for follow-up Exclusion - MGUS or smoldering myeloma - Peripheral sensory neuropathy >= Grade 2 as defined by CTEP Active Version of the CTCAE - Active malignancy with the exception of non melanoma skin cancer or in situ cervical or breast cancer - Pregnant women or women of reproductive ability who are unwilling to use effective contraception - Nursing women - Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment - Known hypersensitivity, allergy or inability to tolerate any of the agents employed - Active, uncontrolled infection - Severe cardiac comorbidity - New York Heart Association Class III or IV Heart Failure - Recent history of myocardial infarction in the six months prior to registration - Uncontrolled angina or electrocardiographic evidence of acute ischemia - Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities - Cardiac amyloidosis with hypotension (systolic BP less than 100 mmHg) - Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment - The following medications are not permitted during the trial: any other investigational treatment; any cytotoxic chemotherapy; any other systemic anti-neoplastic therapy including, but not limited to, immunotherapy, hormonal therapy, or monoclonal antibody therapy - Palliative radiation therapy is permitted if clinically indicated and not indicative of progressive disease |
Country | Name | City | State |
---|---|---|---|
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Mayo Clinic | Rochester | Minnesota |
United States | Mayo Clinic in Arizona | Scottsdale | Arizona |
Lead Sponsor | Collaborator |
---|---|
Mayo Clinic |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Tolerated Dose (Phase I) | 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 |
From baseline to end of active treatment, up to 12 28-day cycles. | |
Primary | Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II) | 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 |
Following the first 4 cycles of treatment (28 day cycles) | |
Secondary | Progression-free Survival (Phase II) | 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 disorder |
From baseline to progression or death up to 3 years | |
Secondary | Time to Treatment Failure | 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 | From baseline to end of active treatment | |
Secondary | Stem Cell Collection and Engraftment (Phase II) | 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. | Following the first 4 courses of treatment | |
Secondary | Complete Response (Phase II) | In patients continuing beyond 4 cycles the ability to induce complete response will be evaluated at completion of planned therapy. | Following the first 4 courses of treatment | |
Secondary | Survival Time (Phase II) | 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 | From baseline to death | |
Secondary | Progression Free Survival (12 Month) | 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. | 12 months | |
Secondary | Progession Free Survival (24 Month) | 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. | 24 months | |
Secondary | Overall Survival (12 Month) | 12 Month Overall survival is defined as the proportion of patients to still be alive after 12 months. | From baseline to death | |
Secondary | Overall Survival (24 Month) | 24 Month Overall survival is defined as the proportion of patients to still be alive after 24 months. | From baseline to death |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05027594 -
Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02412878 -
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
|
Phase 3 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05971056 -
Providing Cancer Care Closer to Home for Patients With Multiple Myeloma
|
N/A | |
Recruiting |
NCT05243797 -
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
|
Phase 3 | |
Active, not recruiting |
NCT04555551 -
MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Recruiting |
NCT03570983 -
A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion
|
Phase 2 | |
Completed |
NCT03665155 -
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
|
Phase 1/Phase 2 | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT02812706 -
Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT05024045 -
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
|
Phase 1 | |
Active, not recruiting |
NCT03792763 -
Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients
|
Phase 2 | |
Active, not recruiting |
NCT03989414 -
A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
|
Phase 1/Phase 2 | |
Withdrawn |
NCT03608501 -
A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation
|
Phase 2 | |
Recruiting |
NCT04537442 -
Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02546167 -
CART-BCMA Cells for Multiple Myeloma
|
Phase 1 |