Vorinostat,Lenalinomide and Dexamethasone in Multiple Myeloma Refractory to Previous Lenalinomide Containing Regimens

NCT01502085 | Completed Phase 1 Results DMC

• 1 other identifier: PRO-2580
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Phase IIb clinical trial to determine if resistance to a lenalidomide containing regimen can be overcome by the addition of vorinostat, in patients with relapsed and refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

multiple myeloma lenalidomide

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (PR or Better) of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed/Refractory MM Refractory to a Previous Lenalidomide Containing Regimen

  Defined as: 1. Progression on therapy OR within 60 days after the last dose of a lenalidomide containing regimen OR 2. No clinical response (\<MR) on a lenalidomide containing regimen An overall response rate of 25% or more will be acceptable, while an overall response of less than or equal to 16% will be considered unacceptable. Response will be assessed according to a modified International Working Group Uniform Response Criteria (Durie et al., 2006) * Complete Response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and ⩽5% plasma cells in bone marrow * Very Good Partial Response- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component \<100 mg per 24 h * Partial Response- ⩾50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ⩾90% or to \<200 mg per 24 h.

  On treatment portion of study is completed after 12 cycles (each cycle is 28 days in duration) and one month of follow up. Patients may be followed for up to two years after last dose of lenalidomide and vorinostat for disease status and survival.

Study Arms (1)

Vorinostat, Lenalinomide, Dexamethasone

EXPERIMENTAL

Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above

Drug: Vorinostat, Lenalinomide and Dexamethasone

Interventions

Vorinostat, Lenalinomide and Dexamethasone DRUG

Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above

Vorinostat, Lenalinomide, Dexamethasone

Eligibility Criteria

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

You may qualify if:

• International Staging System symptomatic multiple myeloma, as recently defined (Kyle et al., 2009) or Durie-Salmon stage I-III multiple myeloma, after at least one (1) prior anti-myeloma regimen.
• Refractory to lenalidomide (administered either with dexamethasone or in combination with other agents); refractory will be defined as no response (\<MR) or PD on or within 60 days of discontinuing a prior lenalidomide-containing regimen.
• Measurable monoclonal protein by serum or urine; or FLC level ≥ 10mg/dL (with abnormal FLC ratio), or measurable extramedullary plasmacytomas:
• No prior HDAC inhibitor
• Age ≥ 18 years
• Performance status ECOG 0-3
• Acceptable organ function as defined by:
• Bilirubin \<2 x upper limit of normal
• ALT and AST \<2.5 x upper limit of normal
• Serum creatinine \<3.0 mg/dL
• ANC ≥1.0 x 109/L
• Platelet count ≥50 x 109/L
• QTc interval ≤ 470ms
• Non-pregnant and non-lactating
• Life expectancy of more than six months

You may not qualify if:

• Subjects with non-secretory or hyposecretory multiple myeloma, defined as \<0.5 g/dL M-protein in serum and \<200 mg/24 hr Bence Jones protein in urine and serum free light chain \<10mg/dL (\<100 mg/L)
• Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation
• Pregnant or breast feeding females
• CrCl \<30 ml/min or renal failure requiring hemodialysis
• Prior history or malignancy other than multiple myeloma, unless patient has been disease free of the disease for ≥3 years.
• Prior or local irradiation within two weeks before screening
• Evidence of central nervous system (CNS) involvement
• Unable to take corticosteroids at study entry
• Peripheral neuropathy of ≥ grade 3 severity
• Inability or unwillingness to comply with birth control requirements
• Unable to take antithrombotic medicines at study entry
• Refusal to participate in study
• Persons protected by a legal regime (guardianship, trusteeship)
• Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 3 weeks prior to first dose
• Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (1)

• Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

  PMID: 16855634 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Vorinostat; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

joshua.zenreich@hmhn.org

551-996-4248

Study Officials

• David Siegel, M.D., Ph.D

  Hackensack Meridian Health

  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: December 27, 2011
• First Posted: December 30, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: January 21, 2022
• Results First Posted: January 21, 2022

Record last verified: 2021-12

Locations

US (1)