- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01889420
Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New Mexico
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Albuquerque, New Mexico, United States, 87131
- UNM Cancer Research and Treatment Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Age > 18 years
Relapsed or progressive multiple myeloma (MM) (Progressive Disease), defined as a 25% increase from the lowest response value in ANY of the following:
Serum M-protein (absolute increase ≥0.5 g/dL)
Urine M-protein (absolute increase of ≥200 mg/24 hours)
Bone marrow plasma cell percentage (≥ 10% absolute increase) in absence of measurable M-protein
Difference in kappa & lambda free light chain levels (ratio must be abnormal; absolute change must be >10 mg/dL)
Patients are also considered to have progressive disease when:
New bone or soft tissue lesions (e.g. plasmacytomas) are identified; or
There is an unequivocal increase in the size of previously existing lesions; or
The development of an otherwise unexplained serum calcium >11.5 mg/dL
Have received 1, but no more than 4 prior treatment regimens or lines of therapy for MM (Induction therapy followed by stem cell transplant & consolidation/maintenance therapy will be considered as one line of therapy)
ECOG Performance status 0 - 2
Life expectancy of at least 12 weeks
Evaluable MM with, at least one of the following, assessed within 21 days prior to randomization:
Serum M-protein ≥ 0.5 g/dL, or Urine M-protein ≥ 200 mg/24 hour, or
In absence of detectable serum or urine M-protein, serum FLC (SFLC) > 100 mg/L (involved light chain) and/or an abnormal kappa/lamda ratio (>4:1 or <2:1), or
Monoclonal plasma cells in a bone marrow biopsy/aspirate of >5%
Adequate organ and marrow function as defined below:
- Leukocytes ≥ 2,500/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin < 2 X ULN
- AST(SGOT)/ALT(SPGT) ≤ 2.5 X ULN
- Creatinine < 1.5 X ULN
Contraception Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for duration of study, and for 90 days after completion of therapy.
A female of child-bearing potential is considered to be any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- No hysterectomy or bilateral oophorectomy; or
- Not naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.
No prior therapy with pomalidomide or everolimus.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Receiving any other investigational agents. Minimum 4 week "washout" period is required.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide, everolimus, or other agents used in the study.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant or nursing (due to the rick for congenital abnormalities and the potential of this regimen to harm nursing infants).
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L.
Waldenstrom's Macroglobulinemia.
Patients with known amyloidosis.
Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).
Immunotherapy within 21 days prior to randomization.
Myelodysplastic syndrome
Major surgery (excluding kyphoplasty) within 28 days
Known cirrhosis.
Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days
Ongoing graft-vs-host disease.
Using CYP3A4 inhibitors such as Ketoconazole, Ritonavir, Itraconazole, Erythromycin, Clarithromycin, Nelfinavir, Fluconazole, Amiodarone, Cyclosporine, Diltiazem, nefazadone,fluvoxamine, verapamil, chloramphenicol, Indinavir or saquinavir within 7 days of treatment.
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: Combination therapy
Pomalidomide: 1 tablet orally, daily for 21 days of a 28 day cycle (dose per cohort) Everolimus: 1 tablet orally for 21 days of a 28 day cycle (dose as per cohort) Dexamethasone 40 mg (20 mg >75yrs) orally, days 1, 8,15, 22 of a 28 day cycle
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Following determination of the maximum tolerated dosages in the phase I portion of this study, all patients enrolled in the extension portion will receive the predetermined dosage combination of pomalidomide, everolimus and dexamethasone. Cycles will span 28 days. Dosage schedules will be:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dosage (MTD)(Phase I)
Time Frame: 2 years
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The Maximum Tolerated Dose (MTD) will be determined by first identifying the dose level at which >= 30% of patients experience a Dose Limiting Toxicity (DLT) according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle.
DLT will be defined based on the rate of drug-related grade 3-5, non-hematological adverse events experienced within the first 4 weeks (1 cycle) for each combined dosage scheme.
The MTD will be defined as one dosage level below which DLT was observed in >= 30% of patients.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity Profile
Time Frame: 2 years
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The toxicity profile will be described by specific adverse event rates among patients experiencing > grade 3 hematologic events (lasting >7 days) or grades 3-5 non-hematologic adverse events, according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle.
Specific events will be described as the numbers of patients experiencing them within each treatment cohort.
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2 years
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Anti-tumor Effect
Time Frame: 3.5 years
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Anti-tumor effect will be assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle. Descriptive statistics will be used for this measurement. Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved. Partial response (PR): >50% reduction in M-protein and >50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by >50%. Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: >25% increase from baseline in serum or urine M-protein (serum M-protein must increase by > 0.5 gm/dl; urine M-protein must increase by >200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (>11.5 mg/dl) attributed to MM. |
3.5 years
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Overall Response Rate (RR)
Time Frame: 3 years
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ORR is the percentage of patients with a > Partial Response (PR). Response is assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle. Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved. PR: >50% reduction in M-protein and >50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by >50%. Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: >25% increase from baseline in serum or urine M-protein (serum M-protein must increase by > 0.5 gm/dl; urine M-protein must increase by >200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (>11.5 mg/dl) attributed to MM. |
3 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ian Rabinowitz, MD, University of New Mexico Cancer Center
- Principal Investigator: Ducinea D Quintana, MD, University of New Mexico Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
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 (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Recurrence
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Pomalidomide
- Everolimus
Other Study ID Numbers
- INST 1304
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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