Trial Outcomes & Findings for Tinostamustine Conditioning and Autologous Stem Cell (NCT NCT03687125)

Last Updated: 2021-06-18

Results Overview

ORR was defined as the participants with a complete response (CR) or very good partial response (VGPR) or partial response (PR) as determined by IMWG Response Criteria. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to less than (\<) 10 mm; PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum longest diameter; VGPR was defined as a \>90% reduction in serum IgM levels from baseline.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

at Day 100 post-autologous stem cell transplant (ASCT)

Results posted on

2021-06-18

Participant Flow

The study was conducted at 3 centers in the United States between 15 October 2018 and 17 April 2019.

A total of 6 participants were enrolled and received study drug in Phase 1. Study was early terminated during Phase 1 due to sponsor decision on 17 April 2019 (adverse events limited administration of higher doses required to achieve myeoblative conditioning necessary in this population). Hence, no participants were enrolled in Phase 2 and efficacy analysis were not performed in the both Phase 1 and 2.

Participant milestones

Participant milestones
Measure	Tinostamustine 180 mg/m^2 Participants received single dose of tinostamustine 180 milligrams per meter square (mg/m\^2) intravenous (IV) injection on Day -1 followed by autologous stem cell transplantation (ASCT) on Day 1.	Tinostamustine 220 mg/m^2 Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Overall Study STARTED	3	3
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Tinostamustine 180 mg/m^2 Participants received single dose of tinostamustine 180 milligrams per meter square (mg/m\^2) intravenous (IV) injection on Day -1 followed by autologous stem cell transplantation (ASCT) on Day 1.	Tinostamustine 220 mg/m^2 Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Overall Study Progressive Disease	2	1
Overall Study Protocol Violation	1	0

Baseline Characteristics

Tinostamustine Conditioning and Autologous Stem Cell

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection followed by autologous stem cell transplantation (ASCT) on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection followed by ASCT on Day 1.	Total n=6 Participants Total of all reporting groups
Age, Continuous	63.3 Years STANDARD_DEVIATION 7.37 • n=5 Participants	61.3 Years STANDARD_DEVIATION 11.02 • n=7 Participants	62.3 Years STANDARD_DEVIATION 8.45 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White/Caucasian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: at Day 100 post-autologous stem cell transplant (ASCT)

Population: The study was early terminated on 17 April 2019, due to safety signals during Phase 1, participants were not enrolled in Phase 2. Hence, no efficacy analysis were analyzed or collected in this study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Phase 1: From Day -1 up to 30 Days post-ASCT

DLT was defined as at least possibly related to tinostamustine based on common terminology criteria for adverse events 4.03 (CTCAE 4.03): (1) delayed engraftment (greater than \[\>\] 30 days after ASCT) where subject has not met criteria for both neutrophil (first of 3 consecutive days with ANC \> 0.5×10\^9/liter \[L\]) and platelet (plt) engraftment (first of 3 consecutive days of plt count \> 20×10\^9/L without plt transfusion in prior 7 days) (2) QTcF \> 500 millisecond (msec) or \> 60 msec increase from baseline with duration of \> 30 minutes or greater than or equal to (\>=) Grade 3 QTcF interval prolongation with ventricular arrhythmia (3) Grade 4 non-hematologic toxicity (4) Grade 3 non-hematologic toxicity related to treatment, except: nausea, emesis, diarrhea, fatigue, dehydration, glucose intolerance, skin rash with treatment, fever (\> 40C for \>= 24 hours), infection, dyspnea, hypoxia, pneumonitis, pain, dysphagia, oral mucositis, anorexia, flu-like or engraftment syndrome, weight.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: at Day 100 post ASCT

ORR for participants who achieved CR, minimal residual disease negativity (MRD-N), was determined by next generation flow cytometry according to the IMWG Criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 6 months

Population: The study was early terminated on 17 April 2019, due to safety signals during Phase 1. Hence, data for this outcome measure was not collected as planned, analyzed and reported at specific time point.

Neutrophil engraftment was defined as the first of 3 consecutive days with absolute neutrophil count (ANC) \>0.5 × 10 \^9/L. Platelet engraftment was defined as the first of 3 consecutive days of platelet count \>20 × 10 \^9/L without platelet transfusion in the prior 7 days. Number of participants with neutrophil and platelet engraftment failure was reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months

Duration of cytopenia i.e ANC \<= 0.5×10\^9/L, and platelet count \<= 20×10\^9/L.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months

Number of participants with treatment related mortality was reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months

Transplant-related non-hematologic grade 3 toxicity was defined by CTCAE 4.03 stratified by hematopoietic cell transplantation comorbidity index (HCT-CI). HCT-CI is a validated comorbidity index that comprises 17 different categories of organ dysfunction. Positive findings are summated into a total score. The HCT-CI provides information with regard to the overall as well as non-relapse mortality risk a patient is likely to experience after stem cell transplantation (SCT).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of tinostamustine up to end of study (up to 6 months)

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) was defined as AE resulting in any of the following outcomes deemed significant for any other reason: death, was life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as an adverse event that started on or after the first dose of tinostamustine through Day 107, or after the end of the study if thought to be related to study drug.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Participants with TEAEs	3 Participants	3 Participants
Phase 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Participants with TESAEs	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (Day -1), Day 30

Hematology parameters assessment included white blood cell (WBC) count and differential (lymphocytes, monocytes, basophils, eosinophils, neutrophils), red blood cell (RBC) count, hematocrit, hemoglobin, and platelet count. Change From baseline in hematology parameters at Day 30 were reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Day -1), Day 100

Clinical serum chemistry tests included electrolytes i.e. bicarbonate, calcium, magnesium, chloride, glucose, phosphate, potassium, and sodium. Change from baseline in clinical serum chemistry tests i.e. electrolytes at Day 100 were reported.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Bicarbonate: Change at Day 100	-0.3 millimoles per liter (mmol/L) Standard Deviation 1.53	-0.7 millimoles per liter (mmol/L) Standard Deviation 1.15
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Calcium: Change at Day 100	0.0667 millimoles per liter (mmol/L) Standard Deviation 0.12332	0.1167 millimoles per liter (mmol/L) Standard Deviation 0.07638
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Chloride: Change at Day 100	-2.3 millimoles per liter (mmol/L) Standard Deviation 4.04	-0.3 millimoles per liter (mmol/L) Standard Deviation 1.53
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Glucose: Change at Day 100	-3.3121 millimoles per liter (mmol/L) Standard Deviation 4.01991	-0.7771 millimoles per liter (mmol/L) Standard Deviation 2.69209
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Magnesium: Change at Day 100	-0.0274 millimoles per liter (mmol/L) Standard Deviation 0.09501	-0.0274 millimoles per liter (mmol/L) Standard Deviation 0.04750
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Phosphate: Change at Day 100	-0.0969 millimoles per liter (mmol/L) Standard Deviation 0.26439	-0.2046 millimoles per liter (mmol/L) Standard Deviation 0.29308
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Potassium: Change at Day 100	0.20 millimoles per liter (mmol/L) Standard Deviation 0.265	0.10 millimoles per liter (mmol/L) Standard Deviation 0.361
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes Sodium: Change at Day 100	-2.0 millimoles per liter (mmol/L) Standard Deviation 3.61	-1.3 millimoles per liter (mmol/L) Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline (Day -1), Day 100

Population: Safety population included all participants who received tinostamustine. The study was early terminated on 17 April 2019, due to safety signals during Phase 1, participants were not enrolled in Phase 2. Here, number analyzed refers to the number of participants with available data for each specified category.

Clinical serum chemistry tests included liver function parameters i.e. Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase, (AST) and Lactate dehydrogenase. Change from baseline in clinical serum chemistry tests i.e. liver function parameters at Day 100 were reported.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters ALT: Change at Day 100	4.0 units per liter (U/L) Standard Deviation 1.73	0.3 units per liter (U/L) Standard Deviation 3.06
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters ALP: Change at Day 100	10.7 units per liter (U/L) Standard Deviation 6.81	14.7 units per liter (U/L) Standard Deviation 5.13
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters AST: Change at Day 100	3.0 units per liter (U/L) Standard Deviation 1.00	2.0 units per liter (U/L) Standard Deviation 4.36
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters Lactate dehydrogenase: Change at Day 100	-21.0 units per liter (U/L) Standard Deviation 11.31	4.0 units per liter (U/L) Standard Deviation 2.83

SECONDARY outcome

Timeframe: Baseline (Day -1), Day 100

Clinical serum chemistry tests included renal function parameters i.e. creatinine and bilirubin. Change from baseline in clinical serum chemistry tests i.e. renal function parameters at Day 100 were reported.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters Creatinine: Change at Day 100	14.1440 millimoles per liter (mmol/L) Standard Deviation 18.71075	25.6360 millimoles per liter (mmol/L) Standard Deviation 8.43282
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters Bilirubin: Change at Day 100	-1.710 millimoles per liter (mmol/L) Standard Deviation 3.4200	-3.420 millimoles per liter (mmol/L) Standard Deviation 6.1655
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters Direct Bilirubin: Change at Day 100	0.855 millimoles per liter (mmol/L) Standard Deviation 1.2092	-3.420 millimoles per liter (mmol/L) Standard Deviation NA NA indicates that standard deviation was not estimated for single participant.
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters Indirect Bilirubin: Change at Day 100	0.855 millimoles per liter (mmol/L) Standard Deviation 1.2092	-6.840 millimoles per liter (mmol/L) Standard Deviation NA NA indicates that standard deviation was not estimated for single participant.

SECONDARY outcome

Timeframe: Baseline (Day -1), Day 100

Clinical serum chemistry tests included total protein. Change from baseline in clinical serum chemistry tests i.e. total protein at Day 100 were reported.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Total Protein	13.67 gram per liter (g/L) Standard Deviation 11.372	30.13 gram per liter (g/L) Standard Deviation 32.309

SECONDARY outcome

Timeframe: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion

Population: Pharmacokinetic (PK) population included all participants in the safety population with at least one quantifiable pre-dose and one quantifiable post-dose PK plasma concentration. The study was early terminated on 17 April 2019, due to safety signals during Phase 1, participants were not enrolled in Phase 2.

Tmax was defined as time to reach maximum plasma concentration. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Tinostamustine and Its Metabolites EDO-S101	0.75 hours Interval 0.5 to 0.75	0.75 hours Interval 0.5 to 0.75
Phase 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Tinostamustine and Its Metabolites M2-EDO-S101	1.00 hours Interval 1.0 to 1.0	1.00 hours Interval 0.75 to 3.0
Phase 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Tinostamustine and Its Metabolites M8-EDO-S101	0.75 hours Interval 0.5 to 0.75	1.00 hours Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion

Population: PK population included all participants in the safety population with at least one quantifiable pre-dose and one quantifiable post-dose PK plasma concentration. The study was early terminated on 17 April 2019, due to safety signals during Phase 1, participants were not enrolled in Phase 2.

Cmax was defined as maximum observed plasma concentration. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Tinostamustine and Its Metabolites M2-EDO-S101	2.85 nanogram per milliliter (ng/mL) Standard Deviation 1.45	2.23 nanogram per milliliter (ng/mL) Standard Deviation 0.633
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Tinostamustine and Its Metabolites M8-EDO-S101	52.4 nanogram per milliliter (ng/mL) Standard Deviation 4.58	60.4 nanogram per milliliter (ng/mL) Standard Deviation 11.5
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Tinostamustine and Its Metabolites EDO-S101	2270 nanogram per milliliter (ng/mL) Standard Deviation 910	3070 nanogram per milliliter (ng/mL) Standard Deviation 1320

SECONDARY outcome

Timeframe: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion

AUC0-t was defined as area under the concentration-time curve from time zero to the last measurable concentration. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tinostamustine and Its Metabolites EDO-S101	2858.44 hournanogram per milliliter (hng/mL) Standard Deviation 1475.82	4922.66 hournanogram per milliliter (hng/mL) Standard Deviation 2056.86
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tinostamustine and Its Metabolites M2-EDO-S101	NA hournanogram per milliliter (hng/mL) Standard Deviation NA Mean and Standard Deviation (SD) was not calculated as data were available for only two participants.	6.65 hournanogram per milliliter (hng/mL) Standard Deviation 3.75
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tinostamustine and Its Metabolites M8-EDO-S101	60.42 hournanogram per milliliter (hng/mL) Standard Deviation 20.36	100.75 hournanogram per milliliter (hng/mL) Standard Deviation 20.01

SECONDARY outcome

Timeframe: Pre-infusion, 0.50, 0.75, 1, 3, 6 hours post-infusion

AUC0-12h was defined as area under the concentration-time curve from time zero to 12 hours. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.

Outcome measures

Outcome measures
Measure	Tinostamustine 180 mg/m^2 n=2 Participants Participants received single dose of tinostamustine 180 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine 220 mg/m^2 n=3 Participants Participants received single dose of tinostamustine 220 mg/m\^2 IV injection on Day -1 followed by ASCT on Day 1.
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of Tinostamustine and Its Metabolites EDO-S101	NA h*ng/mL Standard Deviation NA Mean and SD was not calculated as data were available for only two participants.	4887.16 h*ng/mL Standard Deviation 2052.21

Adverse Events

Tinostamustine (180 mg/m^2)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Tinostamustine (220 mg/m^2)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tinostamustine (180 mg/m^2) n=3 participants at risk Participants received single dose of 180 mg/m\^2 tinostamustine IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine (220 mg/m^2) n=3 participants at risk Participants received single dose of 220 mg/m\^2 tinostamustine IV injection on Day -1 followed by ASCT on Day 1.
Infections and infestations Pneumonia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Cardiac disorders Atrial fibrillation	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.

Other adverse events

Additional Information

Terry Nichols

Mundipharma Research Limited

Phone: (0044)1223424444

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tinostamustine (180 mg/m^2) n=3 participants at risk Participants received single dose of 180 mg/m\^2 tinostamustine IV injection on Day -1 followed by ASCT on Day 1.	Tinostamustine (220 mg/m^2) n=3 participants at risk Participants received single dose of 220 mg/m\^2 tinostamustine IV injection on Day -1 followed by ASCT on Day 1.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Nervous system disorders Headache	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Nervous system disorders Paraesthesia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Nervous system disorders Restless legs syndrome	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Product Issues Thrombosis in device	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Psychiatric disorders Anxiety	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Psychiatric disorders Confusional state	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Psychiatric disorders Insomnia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Renal and urinary disorders Haematuria	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Respiratory, thoracic and mediastinal disorders Nasal dryness	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Skin and subcutaneous tissue disorders Dry skin	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Vascular disorders Hypotension	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Vascular disorders Deep vein thrombosis	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Cardiac disorders Atrial fibrillation	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Nausea	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Constipation	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Dyspepsia	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Anal incontinence	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
General disorders Fatigue	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Infections and infestations Pneumonia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Injury, poisoning and procedural complications Patella fracture	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Electrocardiogram QT prolonged	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	100.0% 3/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Lymphocyte count decreased	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Platelet count decreased	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Blood creatinine increased	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Blood lactate dehydrogenase increased	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Investigations Neutrophil count decreased	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hypokalaemia	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hypocalcaemia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	66.7% 2/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Acidosis	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Diabetes mellitus	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hyperglycaemia	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.	33.3% 1/3 • From first dose of tinostamustine up to end of study (up to 6 months) Safety population included all participants who received tinostamustine.