Multiple Myeloma in RelapsePhase 1/2TITANIUM1NCT03687125
Tinostamustine Conditioning and Autologous Stem Cell
A Phase 1/2 study testing Tinostamustine and Autologous Stem Cell Transplant (ASCT) in people with Multiple Myeloma in Relapse and Multiple Myeloma Progression, run by Mundipharma-EDO GmbH at 12 sites in 3 countries.
Trial summary
Phase 1 The primary objectives of Phase 1 of this study are to: Establish the safety, toxicity, and maximum tolerated dose (MTD) of the tinostamustine conditioning regimen. Identify the recommended Phase 2 dose (RP2D) of tinostamustine for use in the Phase 2 portion of the study. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma in Relapse, Multiple Myeloma Progression, Multiple Myeloma With Failed Remission
- What is being tested?
- Tinostamustine and Autologous Stem Cell Transplant (ASCT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 15 Oct 2018to 17 Apr 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants has Multiple Myeloma (MM) and:
- Has received prior ASCT after standard first-line induction treatment. b. Has evidence of progressive disease (PD), with progression-free interval greater than or equal to (>=) 6 months in Phase 1 >= 18 months in Phase 2.
- Progression Free Interval is defined as the time from date of ASCT to PD. c. Received treatment with lesser than or equal to (<=) 3 prior lines of therapy.
- A line of therapy is defined as 1 or more cycles of a planned treatment program. When participants have undergone sequential phases of treatment without intervening progression, such as induction, collection of peripheral blood stem cells (PBSCs), transplantation and consolidation/maintenance, this is considered to be 1 line of treatment. A new line of therapy is initiated as a result of PD or relapse.
- Complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) to salvage chemotherapy, as determined by the International Myeloma Working Group (IMWG) criteria.
- Is, in the Investigator's opinion, a candidate for consolidation therapy with tinostamustine followed by ASCT. (Note that participants planned to receive tandem ASCT are not eligible for the Phase 1 portion of the study.)
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- Has available autologous peripheral blood stem cell (PBSC) product with CD34 cell dose >= 2×106 cells/kg. The product could be from a collection prior to first ASCT or later second collection. (Note that, although not required, in Phase 1, the Investigator should consider enrolling participant with a large number of available PBSCs to permit subsequent ASCT, as participants in Stage 1 may received a dose lower than that determined to be effective.)
- Age 18-75 years.
- Eastern Cooperative Oncology Group (ECOG) performance status score lesser than (<) 3 at Screening.
- Creatinine clearance >= 40 milliliter per minute (mL/min), as determined by a local laboratory using the Cockcroft-Gault equation within 28 days before ASCT.
- Left ventricular ejection fraction (LVEF) >= 40 percent (%) within 28 days before ASCT.
- Adequate pulmonary function, defined as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) greater than (>) 50% predicted within 28 days before ASCT.
- Adequate liver function, as defined by an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 × the upper limit of normal (ULN) and bilirubin <= 1.5 × ULN within 28 days before ASCT.
- Potassium within the local laboratory's normal range. (Potassium supplementation is permissible.)
Who cannot join
- Participants meeting any of the following criteria are not eligible for study entry:
- History of central nervous system (CNS) disease involvement.
- Primary or secondary plasma cell leukemia at any time point prior to transplant.
- Myocardial infarction (MI) or stroke within 6 months before Screening.
- Uncontrolled acute infection.
- Hematopoietic cell transplantation-comorbidity index (HCT-CI) > 6 points.
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- Concurrent malignant disease with the exception of treated basalioma/spinalioma of the skin or early-stage cervix carcinoma, or early-stage prostate cancer. Previous treatment for other malignancies (not listed above) must have been terminated at least 24 months before registration and no evidence of active disease shall be documented since then.
- Major coagulopathy or bleeding disorder.
- Other serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery.
- Lack of cooperation to allow study treatment as outlined in this protocol.
- Pregnancy or lactating female participants.
- The use of any anti-cancer investigational agents within 21 days prior to the expected start of trial treatment and interval of 14 days to last administration of salvage treatment.
- Receiving treatment with drugs known to prolong the QT/QTc interval.
- QTc interval (Fridericia's formula) > 450 millisecond (msec), based on the mean of triplicate Screening 12-lead electrocardiograms (ECGs).
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
United States7 sites
University of Alabama
Birmingham, Alabama, 35294
Carolinas Healthcare System
Charlotte, North Carolina, 28204
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Kansas Medical Center Kansas City
Kansas City, Kansas, 66160
Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital
Milwaukee, Wisconsin, 53226
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Centre
New York, New York, 10065
Switzerland4 sites
Universitatsspital Basel
Basel
Universitatsspital Bern
Bern
Department of Clinical Research Oncology/Hematology, Kantonsspital St. Gallen
Sankt Gallen
University Hospital Zurich
Zurich
About this study
Official title: Phase 1/2 Open-label Trial of Tinostamustine Conditioning and Autologous Stem Cell Transplantation for Salvage Treatment in Relapsed / Refractory Multiple Myeloma (TITANIUM 1)
Phase 1
The primary objectives of Phase 1 of this study are to:
- Establish the safety, toxicity, and maximum tolerated dose (MTD) of the tinostamustine conditioning regimen.
- Identify the recommended Phase 2 dose (RP2D) of tinostamustine for use in the Phase 2 portion of the study.
The secondary objective of Phase 1 of this study is to:
- Investigate the pharmacokinetics (PK) of tinostamustine.
Read the detailed description
Study Design (Methodology):
This is a 2-part, international, multi-center, open-label study of salvage treatment with tinostamustine conditioning followed by ASCT in participants with relapsed/ refractory multiple myeloma (MM). (ASCT is defined as salvage if the participant had already received a prior ASCT and undergoes a second ASCT after evidence of progressive disease [PD].) Phase 1 of the study employs a standard 3+3 dose escalation design with the objective of defining the dose limiting toxicities (DLTs) of the tinostamustine conditioning regimen and defining the MTD and RP2D for use in the Phase 2 portion of the study.
The Safety Review Committee can make a decision to stop dose escalation or explore intermediary doses at any time. The total dose of tinostamustine will be administered on Day -1. Phase 2 of the study employs a 2-step sequential design (Simon, 1989). In Stage 1 of Phase 2, up to 31 participants initially will be enrolled. If lesser than or equal to (<=) 25 participants of these initial 31 participants experience a response, then no additional participants will be enrolled. However, if greater than (>) 25 participants in Stage 1 of Phase 2 experience a response, then enrollment in this cohort will continue, with up to 71 participants enrolled. In Phase 2 of the study, all participants will receive tinostamustine at the RP2D administered in Phase 1 according to the same schedule. After provision of written informed consent, participants will be screened for study eligibility within 28 days before Day 1 (the day of ASCT). Participants who have a minimum of 2×106 CD34+ cells/kg cryopreserved and are otherwise determined to be eligible, based on screening assessments, will be enrolled and receive the tinostamustine conditioning regimen. The tinostamustine dose will be administered 24 hours pre-ASCT (i.e., Day -1). On Day 1, ASCs will be administered intravenously (IV) according to standard institutional practice. Participants will receive supportive measures (including growth factor support post-ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion, and treatment for neutropenic fever) according to standard institutional practice.
- Conditions
- Multiple Myeloma in Relapse, Multiple Myeloma Progression, Multiple Myeloma With Failed Remission
- Being tested
- Tinostamustine, Autologous Stem Cell Transplant (ASCT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TinostamustineDrug
Participants received tinostamustine IV injection.
Autologous Stem Cell Transplant (ASCT)Procedure or surgery
Undergo autologous stem cell transplant
| Study group | Role | What they receive |
|---|---|---|
| Tinostamustine 180 mg/m^2 | Experimental | 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. Receives: Drug: Tinostamustine; Procedure: Autologous Stem Cell Transplant (ASCT) |
| Tinostamustine 220 mg/m^2 | Experimental | Participants received single dose of tinostamustine 220 mg/m^2 IV injection on Day -1 followed by ASCT on Day 1. Receives: Drug: Tinostamustine; Procedure: Autologous Stem Cell Transplant (ASCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2: Objective Response Rate (ORR) Based on International Myeloma Working Group (IMWG) Response Criteria
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.
Measured: at Day 100 post-autologous stem cell transplant (ASCT)
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)
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.
Measured: Phase 1: From Day -1 up to 30 Days post-ASCT
Secondary outcomes (15)
Phase 1 and 2: Objective Response Rate (ORR) for Participants Treated at the Recommended Phase 2 Dose (RP2D)
ORR for participants who achieved CR, minimal residual disease negativity (MRD-N), was determined by next generation flow cytometry according to the IMWG Criteria.
Measured: at Day 100 post ASCT
Phase 1 and 2: Number of Participants With Neutrophil and Platelet Engraftment Failure
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.
Measured: up to 6 months
Phase 1 and 2: Duration of Cytopenia
Duration of cytopenia i.e ANC <= 0.5×10^9/L, and platelet count <= 20×10^9/L.
Measured: Up to 6 months
Phase 1 and 2: Number of Participants With Treatment Related Mortality (TRM)
Number of participants with treatment related mortality was reported.
Measured: Up to 6 months
Phase 1 and 2: Number of Participants With Transplant-related Non-hematologic Grade 3 Toxicity
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).
Measured: Up to 6 months
Phase 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
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.
Measured: From first dose of tinostamustine up to end of study (up to 6 months)
Phase 1 and 2: Change From Baseline in Hematology Parameters
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.
Measured: Baseline (Day -1), Day 30
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes
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.
Measured: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters
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.
Measured: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters
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.
Measured: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Total Protein
Clinical serum chemistry tests included total protein. Change from baseline in clinical serum chemistry tests i.e. total protein at Day 100 were reported.
Measured: Baseline (Day -1), Day 100
Phase 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Tinostamustine and Its Metabolites
Tmax was defined as time to reach maximum plasma concentration. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.
Measured: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Tinostamustine and Its Metabolites
Cmax was defined as maximum observed plasma concentration. Tinostamustine (EDO-S101) and its metabolites included M2-EDO-S101 and M8-EDO-S101.
Measured: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
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
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.
Measured: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of Tinostamustine and Its Metabolites
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.
Measured: Pre-infusion, 0.50, 0.75, 1, 3, 6 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2018
- Study start15 Oct 2018
- Primary completion17 Apr 2019
- Study completion17 Apr 2019
Why it stopped: Sponsor decision based on adverse events limiting administration of higher doses required to achieve myeoblative conditioning necessary in this population
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Myeloma in RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase 1 Does escalation followed by Phase 2 Expansion at MTD
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma-EDO GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Parameswaran Hari, MD, Study chair, Study ChairDagmar Hess, Study chair, 2nd Study Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03687125
- Sponsor's protocol ID
- EDO-S101-1004
- Other IDs
- 2018-001907-35, 2018
- Acronym
- TITANIUM1
- Status last verified
- May 2021
- First submitted
- 29 Aug 2018
- Last updated
- 18 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Open-label Trial of Tinostamustine Conditioning and Autologous Stem Cell Transplantation for Salvage Treatment in Relapsed / Refractory Multiple Myeloma (TITANIUM 1)
- ClinicalTrials.gov ID
- NCT03687125
- Acronym / sponsor ID
- TITANIUM1 / EDO-S101-1004
- Conditions
- Multiple Myeloma in Relapse, Multiple Myeloma Progression, Multiple Myeloma With Failed Remission
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision based on adverse events limiting administration of higher doses required to achieve myeoblative conditioning necessary in this population
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Mundipharma-EDO GmbHIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 17 Apr 2019 (actual)
- Study completion
- 17 Apr 2019 (actual)
- First posted
- 27 Sep 2018 (actual)
- Results
- Posted 18 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1
The primary objectives of Phase 1 of this study are to:
- Establish the safety, toxicity, and maximum tolerated dose (MTD) of the tinostamustine conditioning regimen.
- Identify the recommended Phase 2 dose (RP2D) of tinostamustine for use in the Phase 2 portion of the study.
The secondary objective of Phase 1 of this study is to:
- Investigate the pharmacokinetics (PK) of tinostamustine.
Detailed description
Study Design (Methodology):
This is a 2-part, international, multi-center, open-label study of salvage treatment with tinostamustine conditioning followed by ASCT in participants with relapsed/ refractory multiple myeloma (MM). (ASCT is defined as salvage if the participant had already received a prior ASCT and undergoes a second ASCT after evidence of progressive disease [PD].) Phase 1 of the study employs a standard 3+3 dose escalation design with the objective of defining the dose limiting toxicities (DLTs) of the tinostamustine conditioning regimen and defining the MTD and RP2D for use in the Phase 2 portion of the study.
The Safety Review Committee can make a decision to stop dose escalation or explore intermediary doses at any time. The total dose of tinostamustine will be administered on Day -1. Phase 2 of the study employs a 2-step sequential design (Simon, 1989). In Stage 1 of Phase 2, up to 31 participants initially will be enrolled. If lesser than or equal to (<=) 25 participants of these initial 31 participants experience a response, then no additional participants will be enrolled. However, if greater than (>) 25 participants in Stage 1 of Phase 2 experience a response, then enrollment in this cohort will continue, with up to 71 participants enrolled. In Phase 2 of the study, all participants will receive tinostamustine at the RP2D administered in Phase 1 according to the same schedule. After provision of written informed consent, participants will be screened for study eligibility within 28 days before Day 1 (the day of ASCT). Participants who have a minimum of 2×106 CD34+ cells/kg cryopreserved and are otherwise determined to be eligible, based on screening assessments, will be enrolled and receive the tinostamustine conditioning regimen. The tinostamustine dose will be administered 24 hours pre-ASCT (i.e., Day -1). On Day 1, ASCs will be administered intravenously (IV) according to standard institutional practice. Participants will receive supportive measures (including growth factor support post-ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion, and treatment for neutropenic fever) according to standard institutional practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase 1 Does escalation followed by Phase 2 Expansion at MTD
| Arm | Type | Receives |
|---|---|---|
| Tinostamustine 180 mg/m^2 | Experimental | Drug: Tinostamustine, Procedure: Autologous Stem Cell Transplant (ASCT)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 | Experimental | Drug: Tinostamustine, Procedure: Autologous Stem Cell Transplant (ASCT)Participants received single dose of tinostamustine 220 mg/m^2 IV injection on Day -1 followed by ASCT on Day 1. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Participants has Multiple Myeloma (MM) and:
- Complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) to salvage chemotherapy, as determined by the International Myeloma Working Group (IMWG) criteria.
- Is, in the Investigator's opinion, a candidate for consolidation therapy with tinostamustine followed by ASCT. (Note that participants planned to receive tandem ASCT are not eligible for the Phase 1 portion of the study.)
- Has available autologous peripheral blood stem cell (PBSC) product with CD34 cell dose >= 2×106 cells/kg. The product could be from a collection prior to first ASCT or later second collection. (Note that, although not required, in Phase 1, the Investigator should consider enrolling participant with a large number of available PBSCs to permit subsequent ASCT, as participants in Stage 1 may received a dose lower than that determined to be effective.)
- Age 18-75 years.
Key exclusion criteria (14 listed)
- History of central nervous system (CNS) disease involvement.
- Primary or secondary plasma cell leukemia at any time point prior to transplant.
- Myocardial infarction (MI) or stroke within 6 months before Screening.
- Uncontrolled acute infection.
- Hematopoietic cell transplantation-comorbidity index (HCT-CI) > 6 points.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TinostamustineParticipants received tinostamustine IV injection. | Drug | Tinostamustine 180 mg/m^2, Tinostamustine 220 mg/m^2 |
| Autologous Stem Cell Transplant (ASCT)Undergo autologous stem cell transplant | Procedure or surgery | Tinostamustine 180 mg/m^2, Tinostamustine 220 mg/m^2 |
Primary outcome
Phase 2: Objective Response Rate (ORR) Based on International Myeloma Working Group (IMWG) Response Criteria
Time frame: at Day 100 post-autologous stem cell transplant (ASCT)
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.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)
Time frame: 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.
15 secondary outcomes
Phase 1 and 2: Objective Response Rate (ORR) for Participants Treated at the Recommended Phase 2 Dose (RP2D)
Time frame: at Day 100 post ASCT
Phase 1 and 2: Number of Participants With Neutrophil and Platelet Engraftment Failure
Time frame: up to 6 months
Phase 1 and 2: Duration of Cytopenia
Time frame: Up to 6 months
Phase 1 and 2: Number of Participants With Treatment Related Mortality (TRM)
Time frame: Up to 6 months
Phase 1 and 2: Number of Participants With Transplant-related Non-hematologic Grade 3 Toxicity
Time frame: Up to 6 months
Phase 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of tinostamustine up to end of study (up to 6 months)
Phase 1 and 2: Change From Baseline in Hematology Parameters
Time frame: Baseline (Day -1), Day 30
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Electrolytes
Time frame: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Liver Function Parameters
Time frame: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Renal Function Parameters
Time frame: Baseline (Day -1), Day 100
Phase 1 and 2: Change From Baseline in Clinical Serum Chemistry Tests: Total Protein
Time frame: Baseline (Day -1), Day 100
Phase 1 and 2: Time to Reach Maximum Plasma Concentration (Tmax) of Tinostamustine and Its Metabolites
Time frame: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
Phase 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Tinostamustine and Its Metabolites
Time frame: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
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
Time frame: Pre-infusion, 0.50, 0.75, 1, 3, 6, 24, 48 hours post-infusion
Phase 1 and 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of Tinostamustine and Its Metabolites
Time frame: Pre-infusion, 0.50, 0.75, 1, 3, 6 hours post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Low-Dose TBI Plus CAR T-Cell Therapy for Relapsed/Refractory DLBCL and Multiple Myeloma
Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed or Refractory Multiple Myeloma (MM)
RecruitingPhase 1/2
Phase 1/2 Study of Linvoseltamab in Adult Patients With Relapsed or Refractory Multiple Myeloma
Multiple Myeloma
RecruitingPhase 2
18F-Fluciclovine PET/CT in Multiple Myeloma
Multiple Myeloma, Newly Diagnosed Multiple Myeloma (NDMM)
Active, not recruitingPhase 2
A Study to Investigate Subcutaneous Isatuximab in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma
Plasma Cell Myeloma Refractory
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parameswaran Hari, MD study chair
Study Chair
Dagmar Hess study chair
2nd Study Chair
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tinostamustine and Autologous Stem Cell Transplant (ASCT) in people with Multiple Myeloma in Relapse and Multiple Myeloma Progression, run by Mundipharma-EDO GmbH at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Switzerland, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 2: Objective Response Rate (ORR) Based on International Myeloma Working Group (IMWG) Response Criteria (time frame: at Day 100 post-autologous stem cell transplant (ASCT)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.