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

Phase 1/Phase 2
18 Years
Not Enrolling
Relapsed/Refractory Multiple Myeloma

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Trial Information

Phase I/II Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory 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.

Inclusion Criteria:

Age > 18 years

Patients with relapsed or progressive multiple myeloma (Progressive Disease), defined as a
25 percent 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 (at least 10 percent absolute increase) in patients who
lack measurable M protein levels

Difference in the kappa and lambda FLC levels (FLC ratio must be abnormal and absolute
change must be >10 mg/dL)

Patients are also considered to have progressive disease when:

New bone or soft tissue lesions (eg, 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 is also a marker of

Patients have received 1, but no more than 4 prior treatment regimens or lines of therapy
for multiple myeloma. (Induction therapy followed by stem cell transplant and
consolidation/maintenance therapy will be considered as one line of therapy)

ECOG Performance status 0 - 2

Patients must have a life expectancy of at least 12 weeks

Patients must have evaluable multiple myeloma 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 patients without detectable serum or urine M-protein, serum free light chain (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


- Creatinine < 1.5 X ULN

Contraception Women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study participation, and for 90 days following completion of
therapy. Should a woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately.

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:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been 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

No prior therapy with pomalidomide or everolimus.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Patients who 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.

Patients may not be receiving any other investigational agents. A 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.

Patients must not be pregnant or nursing due to the potential 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

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes).

Plasma cell leukemia or circulating plasma cells ≥ 2 × 109/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.

Patients with myelodysplastic syndrome.

Major surgery (excluding kyphoplasty) within 28 days prior to randomization.

Patients with known cirrhosis.

Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to

Female patients who are pregnant or lactating.

Ongoing graft-vs-host disease.

Patients taking CYP3A4 inhibitors such as Ketoconazole, Ritonavir, Itraconazole,
Erythromycin, Clarithromycin, Nelfinavir, Fluconazole, Amioderone, Cyclosporine,
Diltiazem, nefazadone,fluvoxamine, verapamil, chloramphenicol, Indinavir or saquinavir
within 7 days of treatment.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dosage (MTD)(Phase I)

Outcome Description:

During the Phase 1 portion of this study, our primary objective is to determine the MTD for combination pomalidomide, dexamethasone and everolimus in patients with refractory or relapsed multiple myeloma in a maximum of 36 patients. This will be determined by first identifying the dose level at which > 30% of patients experienced a DLT according to CTCAE v. 4.0 over a 28 day cycle. The dose combination (or MTD) used for phase 2 portion will be defined as one dosage level below this level.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Ian Rabinowitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of New Mexico Cancer Center


United States: Food and Drug Administration

Study ID:

INST 1304



Start Date:

August 2013

Completion Date:

August 2015

Related Keywords:

  • Relapsed/Refractory Multiple Myeloma
  • myeloma
  • relapse
  • refractory
  • relapsed
  • pomalidomide
  • Pomalyst
  • everolimus
  • Affinitor
  • dexamethasone
  • Multiple Myeloma
  • Neoplasms, Plasma Cell