NCT01889420 · REGISTRY CONDITION SEARCH

Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2015-07-31

This study is being conducted to test the possibility that a combination of three drugs, pomalidomide and everolimus with dexamethasone, may improve patient responses when compared with use of either drug alone, with dexamethasone in refractory/relapsed multiple myeloma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Maximum Tolerated Dosage (MTD)(Phase I)

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outcome · NOT POSTED

Toxicity Profile

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outcome · POSTED

Anti-tumor Effect

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outcome · POSTED

Overall Response Rate (RR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: Combination therapy
label
Combination therapy
type
EXPERIMENTAL

interventions

arm Group Labels
Combination therapy
description
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: 1. Everolimus daily for 28 days of a 28 day cycle; 2. Pomalidomide daily for 21 days of a 28 day cycle 3. Dexamethasone once weekly (on days 1,8,15,22) of a 28 day cycle.
name
Combination therapy
other Names
Pomalyst
Afinitor
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Maximum Tolerated Dosage (MTD)(Phase I)
time Frame
2 years

secondary Outcomes

description
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.
measure
Toxicity Profile
time Frame
2 years
description
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.
measure
Anti-tumor Effect
time Frame
3.5 years
description
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.
measure
Overall Response Rate (RR)
time Frame
3 years

Full study description

brief Summary: This study is being conducted to test the possibility that a combination of three drugs, pomalidomide and everolimus with dexamethasone, may improve patient responses when compared with use of either drug alone, with dexamethasone in refractory/relapsed multiple myeloma.
detailed Description: Given that pomalidomide is an FDA approved drug for patients with relapsed or progressive myeloma, and everolimus has been shown to have single agent activity in relapsed myeloma, it seems reasonable to combine these two active drugs in patients with relapsed/refractory disease. Given that low dose dexamethasone dramatically improved the response rate of pomalidomide, this drug will be added to the combination.

Source references