RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

NCT00809185 | Terminated Phase 2 Results DMC

• 3 other identifiers: CASE1905P30CA043703CASE-CCF-8514
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: RAD001(Everolimus) may stop the growth of cancer cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well RAD001(everolimus) works in treating patients with myelodysplastic syndromes.

Conditions

Myelodysplastic Syndromes

Keywords

de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; previously treated myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)

  Major erythroid response: (1) For patients with a baseline hemoglobin less than 11 g/dL, a major erythroid response is defined as a \> 2 g/dL increase in hemoglobin from baseline; or (2) 100% decrease in red blood cell transfusion requirements. Minor erythroid response: (1) For patients with baseline hemoglobin less than 11 g/dL, a minor erythroid response is defined as an increase in hemoglobin greater than 1 g/dL but less than 2 g/dL from baseline; or (2) \> 50% decrease in red blood cell transfusion requirements.

  2 years of treatment

Secondary Outcomes (2)

• Number of Dose- and Non-dose-limiting Toxicities

  at end of one cycle (28 days)

• Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy

  at 2 years of treatment

Other Outcomes (1)

• Laboratory Correlates (Cytotoxic T-cell Populations, S6K1 Levels, GSTT-1 Mutations, and Presence or Absence of HLA-DR15)

  at 2 years of treatment

Study Arms (1)

RAD001 (everolimus)

EXPERIMENTAL

RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis

Drug: everolimus; Other: laboratory biomarker analysis; Procedure: Bone marrow aspirate/biopsy

Interventions

everolimus DRUG

Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.

Also known as: RAD001

RAD001 (everolimus)

laboratory biomarker analysis OTHER

Laboratory correlates (cytotoxic t cell populations, S6K1 levels, GSTT-1 mutations, and the presence or absence of HLA-DR15) will be assessed to see if any of these correlates correspond to response.

RAD001 (everolimus)

Bone marrow aspirate/biopsy PROCEDURE

Bone marrow aspirate and biopsy with cytogenetics should be obtained within 4 weeks prior to starting drug and at week 33. A bone marrow aspirate and biopsy should also be obtained for patients going off study prior to week 33 (including cytogenetics). The percentage of blasts on the aspirate should be used to determine the IPSS score.

RAD001 (everolimus)

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Low or intermediate-1 risk myelodysplastic syndromes by International Prognostic Scoring System (IPSS) criteria * IPSS score \< 1.5 * Requiring transfusion of 2 units of red blood cells at least once a month (four weeks prior to accrual on study) * High levels of endogenous epoetin alfa (i.e., \> 200 mU/mL) * Unlikely to respond to epoetin alfa, or has a documented clinical non-response to epoetin alfa (at a dose of ≥ 40,000 U weekly) or darbepoetin alfa (at a dose \> 200 mcg every other week) (i.e., \< 2 g/dL increase in hemoglobin and no decrease in transfusion requirements after at least 4 weeks of treatment) * No chronic myelomonocytic leukemia PATIENT CHARACTERISTICS: * ECOG Performance Status of 0-2 * Liver enzymes (AST and ALT) and total bilirubin ≤ 2 times upper limit of normal * Serum creatinine ≤ 2 times upper limits of normal * No clinically significant anemia due to iron, B12, or folate deficiencies; autoimmune or hereditary hemolysis; or gastrointestinal bleeding * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other serious or poorly controlled medical condition that could be exacerbated by or complicate compliance with study therapy PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior treatment (including growth factors) * No chronic use (\> 2 weeks) of physiologic doses of a corticosteroid agent (dose equivalent to \> 10 mg/day of prednisone) within 28 days of the first day of study drug * No concurrent use of another investigational agent * No concurrent therapy with any cytotoxic drugs, steroids, or growth factors

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• Advani AS, Mahfouz RZ, Maciejewski J, Rybicki L, Sekeres M, Tripp B, Kalaycio M, Bates J, Saunthararajah Y. Ribosomal S6 kinase and AKT phosphorylation as pharmacodynamic biomarkers in patients with myelodysplastic syndrome treated with RAD001. Clin Lymphoma Myeloma Leuk. 2014 Apr;14(2):172-177.e1. doi: 10.1016/j.clml.2013.10.001. Epub 2013 Nov 11.

  PMID: 24332215 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Everolimus; Biopsy

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The trial was stopped early due to slow accrual. 18-33 patients were needed to address objectives, however only 7 patients were enrolled. Insufficient patients responded to the treatment to allow laboratory correlates with response to be analyzed.

Results Point of Contact

• Title: Anjali Advani
• Organization: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

advania@ccf.org

216-445-9354

Study Officials

• Anjali Advani, MD

  Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2008
• First Posted: December 17, 2008
• Study Start: November 1, 2005
• Primary Completion: February 1, 2009
• Study Completion: March 1, 2009
• Last Updated: March 7, 2019
• Results First Posted: May 4, 2012

Record last verified: 2019-02

Locations

US (1)