Clinical trial NCT03687125 (phase 1/phase 2, status: terminated)
Conditions: multiple myeloma in relapse, multiple myeloma progression, multiple myeloma with failed remission
ICD codes: C90.02
Drugs: treatment with tinostamustine
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1
Reason stopped: 
    sponsor decisionbased on adverse events limiting administration of higher doses required to
    achieve myeoblative conditioning necessary in this population
  
Eligibility criteria:

        Inclusion Criteria:

          1. Patient has MM and:

               1. Has received prior ASCT after standard first-line induction treatment.

               2. Has evidence of PD, with progression-free interval ≥6 months in Phase 1 ≥18
                  months in Phase 2.

                  Progression Free Interval is defined as the time from date of ASCT to PD.

               3. Received treatment with ≤3 prior lines of therapy. A line of therapy is defined
                  as 1 or more cycles of a planned treatment program. When patients have undergone
                  sequential phases of treatment without intervening progression, such as
                  induction, collection of peripheral blood stem cells, 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 (Garderet et al, 2017).

          2. CR, VGPR, PR, or minimal response (MR) to latest of salvage chemotherapy at relapse,
             as determined by the International Myeloma Working Group (IMWG) criteria.

          3. Is, in the Investigator's opinion, a candidate for consolidation therapy with
             tinostamustine followed by ASCT. (Note that patients planned to receive tandem ASCT
             are not eligible for the Phase 1 portion of the study.)

          4. 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 patient with a large number of available PBSCs to permit
             subsequent ASCT, as patients in Stage 1 may received a dose lower than that determined
             to be effective.)

          5. Age 18-75 years.

          6. Eastern Cooperative Oncology Group (ECOG) performance status score <3 at Screening.

          7. Creatinine clearance ≥40 mL/min, as determined by a local laboratory using the
             Cockcroft-Gault equation within 28 days before ASCT.

          8. Left ventricular ejection fraction (LVEF) ≥40% within 28 days before ASCT.

          9. Adequate pulmonary function, defined as forced expiratory volume in 1 second (FEV1),
             forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) >50%
             predicted within 28 days before ASCT.

         10. 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.

         11. Potassium within the local laboratory's normal range. (Potassium supplementation is
             permissible.)

        Exclusion Criteria:

        Patients meeting any of the following criteria are not eligible for study entry:

          1. History of central nervous system (CNS) disease involvement.

          2. Primary or secondary plasma cell leukemia at any time point prior to transplant

        2. Myocardial infarction (MI) or stroke within 6 months before Screening. 3. Uncontrolled
        acute infection. 4. HCT-CI >6 points. 5. 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.

        6. Major coagulopathy or bleeding disorder. 7. 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.

        8. Lack of cooperation to allow study treatment as outlined in this protocol. 9. Pregnancy
        or lactating female patients. 10. 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.

        11. Receiving treatment with drugs known to prolong the QT/QTc interval. 12. QTc interval
        (Fridericia's formula) >450 msec, based on the mean of triplicate Screening 12-lead ECGs.

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