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

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ClinicalTrials.gov Identifier: NCT02186834
Recruitment Status : Active, not recruiting
First Posted : July 10, 2014
Results First Posted : February 19, 2019
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Selinexor Drug: Liposomal doxorubicin Drug: Dexamethasone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigator-Initiated Phase I/II Clinical Trial of Selinexor (KPT-330) and Liposomal Doxorubicin for Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : September 19, 2014
Actual Primary Completion Date : November 8, 2017
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: 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.

Drug: Selinexor
Selinexor orally as outlined in the study treatment arm.
Other Name: KPT-330

Drug: Liposomal doxorubicin
Pegylated liposomal doxorubicin at a starting dose of 20 mb/m² as outlined in the treatment arm.
Other Names:
  • Lipodox
  • LD

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.
Other Name: Decadron




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: Up to 12 months ]

    Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m^2 and Dexamethasone 40 mg.

    Dose level 1: 40 mg in combination with Lipodox and Dexamethasone.

    Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.

    Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone.

    Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.


  2. Overall Response Rate (ORR) - All Participants [ Time Frame: Up to 24 months ]
    ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): >/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.

  3. Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose [ Time Frame: Up to 24 months ]
    Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): >/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02186834


Locations
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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Karyopharm Therapeutics Inc
Investigators
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Principal Investigator: Rachid Baz, M.D. H. Lee Moffitt Cancer Center and Research Institute
  Study Documents (Full-Text)

Documents provided by H. Lee Moffitt Cancer Center and Research Institute:

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02186834     History of Changes
Other Study ID Numbers: MCC-17814
First Posted: July 10, 2014    Key Record Dates
Results First Posted: February 19, 2019
Last Update Posted: August 28, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Relapsed
Refractory
Myeloma
Additional relevant MeSH terms:
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Doxorubicin
Liposomal doxorubicin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents