- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01842308
Carfilzomib and Melphalan Before Stem Cell Transplant in Treating Patients With Multiple Myeloma
A Phase 1/2 Trial of Carfilzomib and Melphalan and Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma (CARAMEL)
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of carfilzomib that can be added to high dose melphalan as part of conditioning chemotherapy for myeloma. (Phase I) II. To determine the efficacy of the combination in patients with myeloma undergoing stem cell transplantation, as defined by achievement of complete response (CR). (Phase II)
SECONDARY OBJECTIVES:
I. To examine the toxicities associated with addition of carfilzomib to high dose melphalan in patients with multiple myeloma (MM).
II. To determine the progression free rate at 1 and 2 years post registration.
TERTIARY OBJECTIVES:
I. To determine the proportion of patients achieving a minimal residual disease (MRD) negative status.
II. To assess the HevyLite assay prior to and during treatment.
OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study.
CONDITIONING: Patients receive carfilzomib intravenously (IV) over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3.
TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.
After completion of study treatment, patients are followed up at day 30, day 100, and then every 90 days for up to 5 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Serum creatinine =< 2 mg/dL
- Absolute neutrophil count >= 1000/uL
- Platelet count >= 50,000/uL
- Hemoglobin >= 8.0 g/dL
- Diagnosis of symptomatic MM
Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:
- Serum monoclonal protein >= 1.0 g/dL
- >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Serum immunoglobulin free light chain >=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Bone marrow plasma cells >= 30%
- NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis
- NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy
- Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m^2)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)
- Provide informed written consent
- Ejection fraction >= 45%
- Corrected pulmonary diffusion capacity of greater than or equal to 50%
- Forced expiratory volume in 1 second (FEV1) >= 50%
- Forced vital capacity (FVC) >= 50%
- Negative pregnancy test performed =< 7 days prior to registration, for women of childbearing potential only
Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida for treatment
- Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
- Willing to provide blood and bone marrow samples for correlative research purposes
Exclusion Criteria:
- Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant
- More than two prior regimens for therapy of MM
- Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV)
- Other active malignancy < 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
Any of the following:
- Pregnant women or women of reproductive capability 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 28 days after stopping treatment
- Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
- 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
- Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment
CONDITIONING: Patients receive carfilzomib IV over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3. TRANSPLANT: Patients undergo autologous stem cell transplant on day 0. |
Correlative studies
Given IV
Other Names:
Undergo autologous stem cell transplant
Other Names:
Undergo autologous stem cell transplant
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level
Time Frame: Up to day 30
|
Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity(DLT) in at least one-third of patients.
For this study, a DLT is any of the following during the first 2 cycles of treatment; Absolute neutrophil count engraftment* delayed beyond day 21 or Platelet engraftment* delayed beyond day 30, grade 3+ related sensory or motor neuropathy, or grade 4+ related non-neurologic or non-hematologic adverse event(excluding nausea, vomiting, and diarrhea.
Reported below are the number of patients who experienced a DLT.
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Up to day 30
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Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)
Time Frame: Up to 5 years
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The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients.
Exact binomial 95% confidence intervals for the true success percentages will be calculated.
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Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time Frame: Up to 5 years
|
These results are reported in the adverse events section.
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
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Up to 5 years
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Complete Response Rate at Day 100
Time Frame: At day 100
|
Complete response rate (CRR) is defined as the percentage of complete responses estimated by the total number of patients who achieve a complete response by day 100 post-transplant divided by the total number of evaluable patients.
Exact binomial 95% confidence intervals for the true complete response rate at day 100 will be calculated.
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At day 100
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Progression Free Percentage at 1 and 2 Years Post Registration
Time Frame: At 1 year and 2 years
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Progression is an Increase of 25% from lowest value in any of the following (A "25% increase" refers to M protein, FLC and bone marrow results and does not refer to bone lesions, soft tissue plasmacytoma or hypercalcemia.
The lowest value does not need to be a confirmed value.
If the lowest serum Mprotein is ≥ 5 g/dL, an increase in serum M-protein of ≥ 1 g/dL is sufficient to define disease progression.),
(In the case where a value is felt to be a spurious result per physician discretion (for example, a possible lab error), that value will not be considered when determining the lowest value.):
Serum M-protein (absolute increase must be ≥ 0.5 g/dL) and/or Urine M-protein (absolute increase must be ≥ 200 mg/24 hrs) and/or If the only measurable disease is FLC, the difference between involved and uninvolved FLC levels (absolute increase must be>10 mg/dL) and/or If the only measurable disease is BM, bone marrow PC percentage (absolute increase must be ≥ 10%) (Bone marrow criteria for PD
|
At 1 year and 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Suzanne Hayman, Mayo Clinic
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Melphalan
- Mechlorethamine
- Nitrogen Mustard Compounds
Other Study ID Numbers
- MC1185 (Other Identifier: Mayo Clinic)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2013-00550 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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