Clinical trial NCT02978235: A Dose Finding Study Followed by a Safety and Efficacy Study for Patients With Multiple Myeloma or Lymphoma
Official title: A Phase 1, Open-Label Safety, Pharmacokinetic and Efficacy Study of TAS4464 in Patients With Multiple Myeloma or Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
NonHodgkin Lymphoma
Keywords: Multiple Myeloma
Relapsed/Refractory
Lymphoma
Non-Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma
DLBCL
Mantle Cell Lymphoma
MCL
Peripheral T-Cell Lymphoma
PTCL
TAS4464
NEDD8
NAE inhibitor
Neoplasms
Hematologic Diseases
Myeloma
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-30
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The Phase 1 portion of this study will determine the safety of TAS4464 and the most appropriate dose for patients with Multiple Myeloma or Lymphoma.

Detailed description: The trial was put on Clinical Hold prior to Phase 2 due to cases of drug induced liver injury meeting the criteria for Hy's Law.

Background and Rationale:

• TAS4464 is an investigational NEDD8 activating enzyme (NAE) inhibitor, a compound which may affect cancer cell growth and survival. Thus, TAS4464 may help in the treatment of cancer.

Phase 1:

Primary:

* To investigate the safety and tolerability of TAS4464
* To identify a tolerated dose of TAS4464

Secondary:

* To investigate the preliminary efficacy of TAS4464
* To investigate the pharmacokinetics (PK) and the pharmacogenomics (PGx) of TAS4464
* To investigate the pharmacodynamics of TAS4464

Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent
2. Women of child-bearing potential must have a negative pregnancy test

Multiple Myeloma:

Confirmed diagnosis of Multiple Myeloma with measurable disease, having been treated with at least two prior lines of therapy.

Lymphoma:

Confirmed diagnosis of Non-Hodgkin Lymphoma with measurable disease, having been treated with at least one anthracycline-based therapy, with relapse or progression since the last treatment received.

Exclusion Criteria:

1. Any of the following treatments, within the specified time frame, prior to the first dose of TAS4464:

   1. Major surgery within 28 days
   2. Radiation/chemotherapy within 21 days
   3. Monoclonal antibodies within 28 days
   4. Corticosteroid administration \>20 mg/day of prednisone or equivalent within 14 days
   5. Proteasome inhibitors within 14 days
   6. Immunomodulatory agents within 7 days
   7. Stem cell transplant within 3 months
   8. Current immunosuppressive treatment for graft versus host disease
   9. Current use of an investigational agent
2. Active graft versus host disease
3. Known serious illness or medical condition
4. Prior treatment with TAS4464 or known hypersensitivity to any of its inactive ingredients or drugs similar in class
5. Pregnant or breast-feeding female

Primary outcomes:
measure: Number of patients experiencing any dose-limiting toxicities, during dose escalation period, to determine maximum tolerated dose of TAS4464, using NCI CTCAE criteria, laboratory testing, performance status assessments, and other routine visit procedures
timeFrame: Completion of Cycle 1 (28 days)
measure: Efficacy of TAS4464, defined as Objective Response Rate (ORR) per IWG criteria (NHL) and IMWG criteria (MM). This will take into consideration routine assessments including: imaging scans, physical exams, blood tests, urine tests and biopsy results
timeFrame: Up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack Meridian Health
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
Study officials:
References: