Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT02086552 | Completed Phase 2 Results DMC

• 3 other identifiers: MC128BNCI-2014-00170P30CA015083
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well sonidegib and lenalidomide after stem cell transplant works in treating patients with multiple myeloma. Sonidegib and lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and may delay multiple myeloma from coming back after a stem cell transplant.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Complete Response, Assessed Using the International Myeloma Working Group (IMWG) Uniform Response Criteria

  A comfirmed Complete Response (CR) is defined as a CR noted as the objective status on 2 consecutive evaluations. To be categorized as a CR, patients must exhibit the following:\> * Negative immunofixation of serum and urine c, and\> * Disappearance of any soft tissue plasmacytoma, and\> * \<5% plasma cells in Bone Marrow, and\> * If the only measurable disease is the serum free light chain (FLC), a normal FLC ratio.\> We are reporting the proportion of patients achieving a CR or higher divided by the total number of evaluable patients.\> Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 2 years

Secondary Outcomes (3)

• Overall Survival

  Time from SCT to death due to any cause, assessed up to 3 years

• Progression-free Survival (1 Year Survival Rate)

  Time from SCT to progression or death due to any cause, assessed at 1 year

• Progression-free Survival

  Time from SCT to progression or death due to any cause, assessed at 2 years

Other Outcomes (1)

• Proportion of Patients Who Achieve MRD Negative Status

  Up to 3 years

Study Arms (1)

Treatment (sonidegib, lenalidomide)

EXPERIMENTAL

Patients receive sonidegib PO QD on days 1-28 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve sCR, CR, VGPR, PR, MR, or SD (or usCR, uCR, uVGPR, uPR, uMR) continue treatment in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Sonidegib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sonidegib, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (sonidegib, lenalidomide)

Sonidegib DRUG

Given PO

Also known as: ERISMODEGIB, LDE-225, LDE225, Odomzo, Smoothened Antagonist LDE225

Treatment (sonidegib, lenalidomide)

Eligibility Criteria

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

You may qualify if:

• Absolute neutrophil count \>= 1500/uL
• Platelet count \>= 80,000/uL
• Hemoglobin \>= 9.0 g/dL
• Serum total bilirubin =\< 1.5 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN or =\< 5 x ULN if liver involvement
• Plasma creatine phosphokinase (CK) \< 1.5 x ULN
• Serum creatinine =\< 1.5 x ULN or 24-hour clearance \>= 50 ml/min
• Diagnosis of symptomatic multiple myeloma (MM)
• Patients should have received single autologous stem cell transplantation 60-120 days prior to enrollment to the trial
• Patients should have received the autologous SCT within 12 months of their diagnosis of myeloma to be eligible for the study
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care
• Willingness to return to the Mayo Clinic enrolling institution for follow-up
• Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:

You may not qualify if:

• Prior allogeneic bone marrow/peripheral blood stem cell transplant
• Patients with evidence of disease progression post SCT at the time of consideration for the study enrollment will not be included
• Impaired cardiac function or clinically significant heart disease, including any one of the following:
• Angina pectoris within 3 months
• Acute myocardial infarction within 3 months
• Fridericia QT (QTcF) \> 450 msec for males and \> 470 msec for females on the screening electrocardiogram (ECG)
• A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome
• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus type I (HTLV I) or II, hepatitis B virus (HBV), hepatitis C virus (HCV)
• Other active malignancy requiring therapy; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix
• Any of the following:
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 5 mIU/mL)
• Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 6 months after the final dose of study treatment; highly effective contraception is defined as either:
• Total abstinence: when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; sonidegib

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Francis K Buadi, MD
• Organization: Mayo Clinic

Kumar.Shaji@mayo.edu

507/284-2511

Study Officials

• Francis Buadi

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

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: March 11, 2014
• First Posted: March 13, 2014
• Study Start: January 17, 2014
• Primary Completion: January 15, 2018
• Study Completion: August 13, 2021
• Last Updated: December 3, 2021
• Results First Posted: May 29, 2019

Record last verified: 2021-12

Locations

US (1)