Selinexor (KPT-330) and Liposomal Doxorubicin For Relapsed and Refractory Multiple Myeloma

NCT ID: NCT02186834

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-23
• Study Completion Date: 2018-03-14

Brief Summary

The main purpose of this study is to determine the recommended doses of selinexor in combination with liposomal doxorubicin and dexamethasone for patients with relapsed and refractory myeloma. In addition, the study will assess whether this combination with effective for patients with multiple myeloma.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor, Liposomal Doxorubicin and Dexamethasone

Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).

After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor orally as outlined in the study treatment arm.

Liposomal doxorubicin

Intervention Type: DRUG

Pegylated liposomal doxorubicin at a starting dose of 20 mb/m² as outlined in the treatment arm.

Dexamethasone

Intervention Type: DRUG

Participants will be instructed to take Dexamethasone 40 mg (10 tablets) orally once weekly with meals (ideally with breakfast to minimize insomnia). Participants older than 75 years and patients previously intolerant to 40 mg dosage will be allowed to receive 20 mg (5 tablets) once a week.

Interventions

Selinexor

Selinexor orally as outlined in the study treatment arm.

Intervention Type: DRUG

Liposomal doxorubicin

Pegylated liposomal doxorubicin at a starting dose of 20 mb/m² as outlined in the treatment arm.

Intervention Type: DRUG

Dexamethasone

Participants will be instructed to take Dexamethasone 40 mg (10 tablets) orally once weekly with meals (ideally with breakfast to minimize insomnia). Participants older than 75 years and patients previously intolerant to 40 mg dosage will be allowed to receive 20 mg (5 tablets) once a week.

Intervention Type: DRUG

Other Intervention Names

KPT-330; Lipodox; LD; Decadron

Eligibility Criteria

Inclusion Criteria

• Patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies which must include lenalidomide and a proteasome inhibitor. Patients must have disease refractory to the most recent therapy. Refractory myeloma is defined as progressive disease during or within 60 days of last therapy. Patients must have previously received or be ineligible for (or refused) autologous stem cell transplant.
• Must have measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by free light chain (involved free light chain greater than 100 mg/L).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. ECOG 2 allowed if due to bone disease
• Must have an echocardiogram or multigated acquisition (MUGA) scan indicating left ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of study drug
• Adequate hematological function
• Adequate hepatic function within 14 days prior to loading phase (day -14)
• Adequate renal function within 14 days prior to loading: estimated creatinine clearance of ≥ 30 mL/min, (Cockcroft and Gault)
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.

Exclusion Criteria

• Women who are pregnant or lactating
• Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2 weeks prior to day -7 (beginning of loading phase)
• Major surgery within four weeks before Day -7
• Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
• Prior cumulative exposure to doxorubicin (including liposomal preparation) > 350mg/m^2
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
• Known to be HIV seropositive
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or HBsAg (HBV surface antigen)
• Any underlying condition that would significantly interfere with the absorption of an oral medication
• Grade >2 peripheral neuropathy at baseline (within 14 days prior to loading phase (day -7))
• Serious psychiatric or medical conditions that could interfere with treatment
• Participation in an investigational anti-cancer study within 3 weeks prior to day -7(beginning of loading phase)
• Concurrent therapy with approved or investigational anticancer therapeutic
• Coagulation problems and active bleeding in the last month
• Previous allogeneic transplant within 6 months and have evidence of clinically significant graft versus host disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachid Baz, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

References

Turner JG, Dawson JL, Grant S, Shain KH, Dalton WS, Dai Y, Meads M, Baz R, Kauffman M, Shacham S, Sullivan DM. Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors. J Hematol Oncol. 2016 Aug 24;9(1):73. doi: 10.1186/s13045-016-0304-z.

Reference Type: DERIVED

PMID: 27557643 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MCC-17814

Identifier Type: -

Identifier Source: org_study_id