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

NCT01889420 | Terminated Phase 1 Results DMC

• 1 other identifier: INST 1304
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma in Relapse

Keywords

myeloma; relapse; refractory; relapsed; pomalidomide; pomalyst; everolimus; afinitor; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dosage (MTD)(Phase I)

  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.

  2 years

Secondary Outcomes (3)

• Toxicity Profile

  2 years

• Anti-tumor Effect

  3.5 years

• Overall Response Rate (RR)

  3 years

Study Arms (1)

Combination therapy

EXPERIMENTAL

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

Drug: Combination therapy

Interventions

Combination therapy DRUG

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.

Also known as: Pomalyst, Afinitor

Combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead
• Novartis: collaborator

Study Sites (1)

UNM Cancer Research and Treatment Center

Albuquerque, New Mexico, 87131, United States

Location

Related Links

• UNM Cancer Center
• New Mexico Cancer Care Alliance

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Recurrence

Interventions

Combined Modality Therapy; pomalidomide; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

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

Results Point of Contact

• Title: Dulcinea Quintana, MD
• Organization: University of New Mexico

dcandelaria@salud.unm.edu

505-272-4661

Study Officials

• Ian Rabinowitz, MD

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

• Ducinea D Quintana, MD

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: June 28, 2013
• Study Start: July 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 31, 2015
• Results First Posted: July 31, 2015

Record last verified: 2015-07

Locations

US (1)