Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Recurrence

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Disease Attributes

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Dexamethasone

Everolimus

Pomalidomide

Dexamethasone acetate

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

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

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.

Combination therapy

Ian Rabinowitz, MD

Ducinea D Quintana, MD

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.

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.

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

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.

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.

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.

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.

Novartis

New Mexico Cancer Care Alliance

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

Combination therapy: 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.

Combination Therapy

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Low accrual led to early termination; only one subject was enrolled.

Dulcinea Quintana, MD

There was only one patient enrolled. The MTD could not be calculated based on one patient.

Maximum Tolerated Dosage (MTD)(Phase I)

Toxicity Profile

There was only one patient enrolled. Anti-tumor effect cannot be reported accurately based on results from one patient.

Anti-tumor Effect

There was only one patient enrolled. Response rates cannot be accurately reported based on one patient.

Overall Response Rate (RR)

Overall Study

Spots Global Cancer Trial Database for Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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