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

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02186834
• Collaborator: Karyopharm Therapeutics Inc (Industry)
• Enrollment: 28
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 102.2
• Patients Per Site: 14
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• 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: Sep 23, 2014
• Actual Primary Completion Date: Nov 8, 2017
• Anticipated Study Completion Date: Apr 1, 2023

Arms and Interventions

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 Names: 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 Names: Decadron

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
2	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

• Principal Investigator: Rachid Baz, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 31, 2017

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT02186834
• Other Study ID Numbers: MCC-17814
• First Posted: Jul 10, 2014
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• 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: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Recruitment Details	Participants were recruited at Moffitt Cancer Center and Karmanos Cancer Center September 2014 through May 2017.
Pre-assignment Detail	6 of the 14 participants treated at RP2D moved on from Dose 2m arm in the dose escalation portion of study.

Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m	Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D
Arm/Group Description	Dose 1: Participants were administered Lipodox 20 mg/m^2 via IV on Day 1 of cycle. Selinexor at 40 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.	Dose 2: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.	Dose 1m: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 60 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.	Dose 2m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.	Dose 3m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,3, 8 and 10 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.	Phase 2 Dose: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.
Period Title: Dose Escalation
STARTED	6	3	0	7	4	0
COMPLETED	6	3	0	6	4	0
NOT COMPLETED	0	0	0	1	0	0
Period Title: Dose Escalation
STARTED	0	0	0	0	0	14
COMPLETED	0	0	0	0	0	13
NOT COMPLETED	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone
Arm/Group Description	Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)
Overall Participants	27
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	14 51.9%
Male	13 48.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 11.1%
Not Hispanic or Latino	24 88.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 11.1%
White	21 77.8%
More than one race	0 0%
Unknown or Not Reported	2 7.4%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	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.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All participants treated during dose escalation

Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone
Arm/Group Description	Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)
Measure Participants	19
Number [mg]	80

2. Primary Outcome

Title	Overall Response Rate (ORR) - All Participants
Description	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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone
Arm/Group Description	Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)
Measure Participants	27
>/= Very Good Partial Response	2 7.4%
>/= Partial Response	4 14.8%
>/= Minimal Response	9 33.3%
Stable Disease	8 29.6%
Not Evaluable	4 14.8%

3. Primary Outcome

Title	Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose
Description	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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

All participants treated at recommended phase 2 dose, regardless of when they joined the study.

Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone
Arm/Group Description	Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D)
Measure Participants	14
>/= Very Good Partial Response	0 0%
>/= Partial Response	1 3.7%
>/= Minimal Response	2 7.4%
Stable Disease	4 14.8%
Not Evaluable	1 3.7%

Adverse Events

Time Frame	3 years, 2 months
Adverse Event Reporting Description	All Adverse Events (AEs) and Serious Adverse Events (SAEs) at all grade levels, regardless of causality have been reported in this section. One participant died prior to treatment but after consent. Only participants who received treatment were considered at Risk for Serious and Other Adverse Events.
Arm/Group Title	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m		Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D
Arm/Group Description	Dose 1: Participants were administered Lipodox 20 mg/m^2 via IV on Day 1 of cycle. Selinexor at 40 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.		Dose 2: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.		Dose 1m: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 60 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.		Dose 2m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.		Dose 3m: Participants were administered Lipodox 20mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,3, 8 and 10 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.		Phase 2 Dose: Participants were administered Lipodox 20 mg/m^2 on Day 1 of cycle. Selinexor at 80 mg was given orally on days 1,8 and 15 of the cycle. Dexamethasone at 40 mg was given orally on days 1, 8 and 15.
All Cause Mortality
	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m		Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/3 (33.3%)		0/0 (NaN)		1/7 (14.3%)		0/4 (0%)		1/8 (12.5%)
Serious Adverse Events
	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m		Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		1/1 (100%)		0/0 (NaN)		6/7 (85.7%)		0/4 (0%)		0/7 (0%)
Blood and lymphatic system disorders
Anemia	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Blood and lymphatic system disorders - Other	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Cardiac disorders
Atrial fibrillation	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Constipation	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Dental caries	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Diarrhea	2/6 (33.3%)	2	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Fecal incontinence	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Mucositis oral	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Nausea	2/6 (33.3%)	2	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Vomiting	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
General disorders
Chills	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Death	1/6 (16.7%)	1	1/1 (100%)	1	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Edema face	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Edema limbs	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Fever	2/6 (33.3%)	3	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Infections and infestations
Pneumocystitis pneumonia	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Streptococcal pneumonia	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
RSV pneumonia	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Pleural infection	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Sepsis	2/6 (33.3%)	2	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Upper respiratory infection	2/6 (33.3%)	2	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Urinary tract infection	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Investigations
CPK increased	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Platelet count decreased	3/6 (50%)	3	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Musculoskeletal deformity	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Pain in extremity	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Nervous system disorders
Dizziness	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Lethargy	0/6 (0%)	0	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/6 (16.7%)	1	0/1 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Other (Not Including Serious) Adverse Events
	Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 1m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 2m		Selinexor, Liposomal Doxorubicin and Dexamethasone- Dose 3m		Selinexor, Liposomal Doxorubicin and Dexamethasone- RP2D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		3/3 (100%)		0/0 (NaN)		7/7 (100%)		4/4 (100%)		6/7 (85.7%)
Blood and lymphatic system disorders
Anemia	2/6 (33.3%)	7	3/3 (100%)	8	0/0 (NaN)	0	3/7 (42.9%)	3	2/4 (50%)	3	2/7 (28.6%)	2
Febrile neutropenia	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Thrombotic thrombocytopenia purpura	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Cardiac disorders
Ventricular tachycardia	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders - Other	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Eye disorders
Blurred vision	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	2	0/4 (0%)	0	1/7 (14.3%)	1
Cataract	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Watering eyes	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Nausea	4/6 (66.7%)	6	2/3 (66.7%)	2	0/0 (NaN)	0	1/7 (14.3%)	1	3/4 (75%)	3	1/7 (14.3%)	2
Diarrhea	2/6 (33.3%)	6	1/3 (33.3%)	1	0/0 (NaN)	0	2/7 (28.6%)	2	0/4 (0%)	0	0/7 (0%)	0
Vomiting	2/6 (33.3%)	6	1/3 (33.3%)	2	0/0 (NaN)	0	2/7 (28.6%)	4	1/4 (25%)	1	1/7 (14.3%)	2
Mucositis oral	1/6 (16.7%)	1	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Constipation	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	2/7 (28.6%)	2	0/4 (0%)	0	0/7 (0%)	0
Dry Mouth	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Fecal incontinence	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Gastroesophageal reflux disease	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
General disorders
Fatigue	2/6 (33.3%)	4	2/3 (66.7%)	2	0/0 (NaN)	0	2/7 (28.6%)	2	2/4 (50%)	2	3/7 (42.9%)	3
Fever	1/6 (16.7%)	3	1/3 (33.3%)	1	0/0 (NaN)	0	4/7 (57.1%)	5	0/4 (0%)	0	0/7 (0%)	0
Edema limbs	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	2/7 (28.6%)	2	1/4 (25%)	1	0/7 (0%)	0
Flu like symptoms	2/6 (33.3%)	2	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Chills	0/6 (0%)	0	1/3 (33.3%)	3	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
General disorders - Other	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Localized edema	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Pain	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
Infections and infestations
Infections and infestations - Other	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Sinusitis	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Upper Respiratory Infection	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	1/7 (14.3%)	1
Urinary tract infection	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Bronchial infection	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Lung infection	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Pleural infection	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
Skin Infection	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Tooth infection	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Fall	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
Investigations
Platelet count decreased	4/6 (66.7%)	10	3/3 (100%)	12	0/0 (NaN)	0	3/7 (42.9%)	5	1/4 (25%)	1	1/7 (14.3%)	3
White blood cell decreased	5/6 (83.3%)	10	3/3 (100%)	9	0/0 (NaN)	0	3/7 (42.9%)	4	1/4 (25%)	3	0/7 (0%)	0
Neurtrophil count decreased	4/6 (66.7%)	9	3/3 (100%)	5	0/0 (NaN)	0	2/7 (28.6%)	4	1/4 (25%)	1	1/7 (14.3%)	1
Lymphocyte count decreased	3/6 (50%)	5	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Alanine aminotransferase increased	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	1/7 (14.3%)	1
Aspartate aminotransferase increased	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	1/7 (14.3%)	1
Weight loss	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	2/7 (28.6%)	2	0/4 (0%)	0	0/7 (0%)	0
Alkaline phosphatase increased	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Blood bilirubin increased	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
CPK increased	1/6 (16.7%)	2	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Creatinine increased	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	3/6 (50%)	5	2/3 (66.7%)	3	0/0 (NaN)	0	2/7 (28.6%)	5	0/4 (0%)	0	1/7 (14.3%)	1
Anorexia	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	3/7 (42.9%)	3	1/4 (25%)	1	1/7 (14.3%)	1
Hyperglycemia	1/6 (16.7%)	3	1/3 (33.3%)	1	0/0 (NaN)	0	2/7 (28.6%)	2	0/4 (0%)	0	1/7 (14.3%)	1
Dehydration	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	1/7 (14.3%)	2	1/4 (25%)	1	1/7 (14.3%)	1
Hypocalcemia	2/6 (33.3%)	2	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Hypoalbuminemia	1/6 (16.7%)	1	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Hypophosphatemia	1/6 (16.7%)	2	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	2/6 (33.3%)	2	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Arthralgia	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Back Pain	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
General muscle weakness	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
Musculoskeletal and connective tissue disorders -Other	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Osteonecrosis of jaw	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Nervous system disorders
Dysgeusia	0/6 (0%)	0	2/3 (66.7%)	2	0/0 (NaN)	0	2/7 (28.6%)	2	2/4 (50%)	2	0/7 (0%)	0
Amnesia	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Headache	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Lethargy	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Psychiatric disorders
Depression	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Psychiatric disorders - Other	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Renal and urinary disorders
Renal and urinary disorders - Other	1/6 (16.7%)	1	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Renal calculi	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Urinary frequency	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Urinary incontinence	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Reproductive system and breast disorders
Reproductive system and breast disorders - Other	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Adult respiratory distress syndrom	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Epistaxis	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Hiccups	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	1/4 (25%)	1	0/7 (0%)	0
Productive cough	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Respiratory failure	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders -Other	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Erythroderma	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Palmer-plantar erythrodesthesia syndrome	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1
Surgical and medical procedures
Surgical and medical procedures - Other	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Vascular disorders
Thromboembolic event	1/6 (16.7%)	1	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Hot flashes	0/6 (0%)	0	0/3 (0%)	0	0/0 (NaN)	0	1/7 (14.3%)	1	0/4 (0%)	0	0/7 (0%)	0
Hypertension	1/6 (16.7%)	3	0/3 (0%)	0	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0
Hypotension	0/6 (0%)	0	1/3 (33.3%)	1	0/0 (NaN)	0	0/7 (0%)	0	0/4 (0%)	0	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.