Tinostamustine Conditioning and Autologous Stem Cell

• Status: Terminated
• Trial end date: 2019-04-17
• Target enrollment: 0
• Participant gender: All

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.

The secondary objective of Phase 1 of this study is to:

• Investigate the pharmacokinetics (PK) of tinostamustine.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mundipharma-EDO GmbH

Criteria

Inclusion Criteria:

1. Participants has Multiple Myeloma (MM) and:

a. 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.

2. 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.

3. 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.)

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 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.)

5. Age 18-75 years.

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

7. Creatinine clearance >= 40 milliliter per minute (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 percent (%) 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) greater than (>) 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:

Participants 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.

3. Myocardial infarction (MI) or stroke within 6 months before Screening.

4. Uncontrolled acute infection.

5. Hematopoietic cell transplantation-comorbidity index (HCT-CI) > 6 points.

6. 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.

7. Major coagulopathy or bleeding disorder.

8. 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.

9. Lack of cooperation to allow study treatment as outlined in this protocol.

10. Pregnancy or lactating female participants.

11. 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.

12. Receiving treatment with drugs known to prolong the QT/QTc interval.

13. QTc interval (Fridericia's formula) > 450 millisecond (msec), based on the mean of triplicate Screening 12-lead electrocardiograms (ECGs).