Clinical trial NCT00618345: Everolimus in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official title: Phase II Trial of RAD001 in Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: refractory multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-20
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with relapsed or refractory multiple myeloma.

Detailed description: OBJECTIVES:

Primary

* To assess the response rate in patients with relapsed or refractory multiple myeloma treated with everolimus.

Secondary

* To evaluate the toxicity of everolimus in patients with multiple myeloma.
* To study the tumor cells and blood from patients entering this trial for laboratory correlates.

OUTLINE: Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspirate, biopsy, and blood sample collections periodically. Samples are assessed for the following: cyclin D1, phospho-AKT, phospho-p70 S6 kinase, and phospho-S6 by western blot; checkpoint regulators PTEN, p53, pRB, and p27 by immunoblotting; p53, Rb, p16, PTEN, p27, and cyclin D1 by DNA analysis; caspases 3 and 9 by immunoblotting and Annexin/PI by flow cytometry; unknown molecular markers by protein profiling; and microvessel density.

After completion of study treatment, patients are followed every 3-6 months for up to 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of multiple myeloma, meeting 1 of the following criteria:

  * Monoclonal protein in the serum of ≥ 1 g/dL
  * Monoclonal light chain in the urine protein electrophoresis of ≥ 200 mg/24 hours
  * Measurable light chains by free light chain assay of ≥ 10 mg/dL
  * Measurable plasmacytoma
* Must have received prior therapy and have relapsed or refractory disease

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ≥ 12 weeks
* ANC ≥ 1,000/mm³
* Platelet count ≥ 75,000/mm³
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 2.0 mg/dL (if total bilirubin is elevated, direct bilirubin must be normal)
* AST ≤ 3 times upper limit of normal (ULN)
* Creatinine ≤ 1.5 times ULN
* Calcium \< 11 mg/dL
* No uncontrolled infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No HIV positivity

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 3 weeks since prior cytotoxic chemotherapy
* At least 2 weeks since prior biologic therapy or radiotherapy
* At least 2 weeks since prior corticosteroids

  * Concurrent chronic corticosteroids allowed for treatment of disorders other than myeloma
* No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational

Primary outcomes:
measure: Confirmed response (complete response, very good partial response, partial response, or minimal response) of serum and urine monoclonal protein
Secondary outcomes:
measure: Toxicity
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Thomas E. Witzig, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Rafael Fonseca, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Roy Vivek, MD
role: PRINCIPAL_INVESTIGATOR
References: