Clinical Trials /

TEW-7197 in Combination w/ Pomalidomide in Relapsed or Relapsed and Refractory Multiple Myeloma

NCT03143985

Description:

The purpose of this study is to see if the study drug, called TEW-7197, is safe and determine what the best dose is to treat future patients when given in combination with pomalidomide (POM). The study will also look to see if it has any effect on multiple myeloma, when given in combination with POM.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TEW-7197 in Combination w/ Pomalidomide in Relapsed or Relapsed and Refractory Multiple Myeloma
  • Official Title: A Phase I Trial of TEW-7197 in Combination With Pomalidomide (POM) in Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM)

Clinical Trial IDs

  • ORG STUDY ID: CASE1A17
  • NCT ID: NCT03143985

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
TEW-7197EW-7197, EW7197TEW-7197 + Pomalidomide
PomalidomidePOMTEW-7197 + Pomalidomide

Purpose

The purpose of this study is to see if the study drug, called TEW-7197, is safe and determine what the best dose is to treat future patients when given in combination with pomalidomide (POM). The study will also look to see if it has any effect on multiple myeloma, when given in combination with POM.

Detailed Description

      Primary Objective

        -  To determine the maximum tolerated dose (MTD) or maximum tested dose level of TEW-7197
           given in combination with pomalidomide (POM) for the treatment of relapsed or relapsed
           or refractory multiple myeloma (RRMM)

        -  To characterize the safety and tolerability profile of TEW-7197 in combination with POM
           at the MTD

      Secondary Objectives

      To evaluate the activity of the combination of TEW-7197/POM regimen in terms of:

        -  Overall response rate (complete response [CR] + very good partial response [VGPR]
           +partial response [PR]) and clinical benefit rate (CR + VGPR + PR + minimal response
           [MR]) based on International Myeloma Working Group (IMWG) defined response criteria and
           the duration of response (DOR) in RRMM patients.

        -  Progression-free survival (PFS) and PFS at 6 months (PFS-6)

      Exploratory Objective:

      To evaluate the bone remodeling and immunologic effects of POM/TEW combination therapy and
      its correlation with clinical outcome in patients with multiple myeloma.

      Study Design To evaluate the bone remodeling and immunologic effects of POM/TEW combination
      therapy and its correlation with clinical outcome in patients with multiple myeloma. This
      study is a Phase I, open label trial of TEW-7197 in combination with standard doses of POM.
      The study will be conducted as a modified Fibonacci 3 + 3 dose escalation design to determine
      the MTD of TEW-7197 in combination with standard doses of POM. Patients will receive
      combination TEW-7197 /POM.
    

Trial Arms

NameTypeDescriptionInterventions
TEW-7197 + PomalidomideExperimentalTEW-7197 tablets, taken once daily for 5 days followed by 2 days without treatment, repeated for 28-day cycles until appearing evidence of progressive disease or intolerable toxicity, or subject discontinuing the study for other reasons. For dose escalation during this study, dosing will be initiated at 60 mg once daily by oral administration and will be increased to determine the MTD. Provisional subsequent doses are 60, 120, 240 mg once daily on days 1-5, 8-12, 15-19 and 22-26. POM is administered orally (4 mg/day daily on Days 1 - 21 days). Treatment will occur in a suitable outpatient ambulatory care setting that is equipped for monitoring of patients with hematopoietic malignancies undergoing early clinical trial research.
  • TEW-7197
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has given voluntary written informed consent before performance of any
             study-related procedures not part of standard (non-investigational) medical care.

          -  Patient has been previously diagnosed with multiple myeloma based on standard
             criteria.

          -  Patient has relapsed or refractory disease according to international uniform response
             criteria and must have previously received therapy with:

               -  A proteasome inhibitor and Immunomodulatory imide drugs (IMiD)

               -  All subjects must have documented disease progression during or after their last
                  antimyeloma therapy.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.

          -  Patient has measurable disease defined as at least one of the following:

               -  Serum M protein ≥ 0.5 /dL (≥5 g/L)

               -  Urine M protein ≥ 200 mg/24 hours

               -  Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and
                  an abnormal serum FLC ratio (<0.26 or >1.65)

          -  Clinical Laboratory Inclusion Criteria: The following laboratory results must be met
             within 14 days (or as stipulated) prior to study drug (treatment) administration:

               -  Absolute neutrophil count (ANC) ≥ 1000 cells/μl (growth factor cannot be used
                  within the previous 5 days)

               -  Platelet count ≥ 50,000/μl (without platelet transfusion in the previous 5 days)

               -  Aspartate aminotransferase (AST/SGOT) and Alanine aminotransferase (ALT/SGPT) ≤
                  3.0 x upper limit of normal (ULN)

               -  Serum total bilirubin ≤ 2.0 mg/dL or >3.0 x ULN for subjects with hereditary
                  benign hyperbilirubinemia

               -  Creatinine clearance ≥ 30 ml/min (calculated by the Cockcroft-Gault Equation or
                  per 24 hour urine collection)

               -  Serum calcium (corrected for albumin) level at or below the ULN range (treatment
                  of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to
                  normal range with standard treatment).

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test prior to initiation of the study treatment with TEW-7197 /POM. The test must have
             a sensitivity of at least 50 mIU/mL. Study participants who are FCBP must either
             commit to continued abstinence from heterosexual intercourse or begin two acceptable
             methods of birth control, one highly effective method and one additional effective
             method at the same time, at least 28 days before she starts taking POM through 30 days
             after the last dose of POM and 60 days after the last dose of TEW-7197. FCBP must also
             agree to ongoing pregnancy testing during the entire duration of treatment. Men must
             agree to use a latex or synthetic condom during sexual contact with a FCBP even if
             they have had a vasectomy from the time of signing the informed consent form through
             60 days after the last dose of POM or TEW-7197. These same patients must not donate
             sperm. All patients must be counseled at a minimum of every 28 days about pregnancy
             precautions and risks of fetal exposure. All patients enrolled into this trial, must
             agree to be registered in and must comply with all requirements of the Pomalidomide
             Risk Evaluation and Mitigation Strategy (POM REMS™) program.

        Exclusion Criteria:

          -  Prior therapy with TEW-7197 or received any investigational drug within the prior 28
             days.

          -  Plasma Cell Leukemia

          -  Patients with solitary plasmacytoma

          -  Patients who are primarily eligible for autologous stem cell transplant

          -  Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and
             immunotherapy) within the prior 21 days except for alkylating agents (e.g., melphalan)
             within the prior 28 days.

          -  Prior treatment with pomalidomide.

          -  Subjects with active malignancy and/or cancer history that may confound the assessment
             of the study endpoints. Patients with a past cancer history (within 2 years of entry)
             with substantial potential for recurrence and/or ongoing active malignancy must be
             discussed with the trial collaborator, MedPacto Inc., before study entry. Patients
             with the following neoplastic diagnoses are eligible: non-melanoma skin cancer,
             carcinoma in situ (including superficial bladder cancer), cervical intraepithelial
             neoplasia, and organ-confined prostate cancer with no evidence of progressive disease

          -  Any > grade 1 (according to the National Cancer Institute Common Terminology Criteria
             for Adverse Events (NCI CTC AE) v.4.03) adverse reaction unresolved from previous
             treatments or not readily managed and controlled with supportive care. The presence of
             alopecia of any grade and peripheral neuropathy ≤ Grade 2 without pain is allowed.

          -  Previous allogeneic stem cell transplantation with active graft versus host disease
             (GVHD), or treatment with immunosuppressive therapy in the 2 months prior to study
             entry.

          -  No oral corticosteroids 3 days before initiating combinations TEW-7197/POM; inhaled
             corticosteroids are permitted.

          -  Patient is known to be human immunodeficiency virus (HIV) positive, or have chronic or
             active Hepatitis B (core- or surface antigen-positive) or active hepatitis C
             infection.

          -  Clinically significant cardiovascular disease (e.g., uncontrolled or any New York
             Heart Association (NYHA) Class 3 or 4, congestive heart failure, uncontrolled or
             unstable angina, history of myocardial infarction or stroke within 6 months prior to
             study entry, or clinically significant arrhythmias not controlled by medication).

          -  Major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's
             discretion.

          -  Presence of aneurisms of the ascending aorta or aortic stress.

          -  Hypertension that is not controlled by standard medication (to 150/90 mmHg or below).

          -  Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive
             pulmonary disease (COPD), pulmonary hypertension) that in the opinion of the
             investigator would put the patient at significant risk for pulmonary complications
             during the study.

          -  Uncontrolled intercurrent illness including, but not limited to, uncontrolled
             infection, disseminated intravascular coagulation (DIC), or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  History of erythema multiforme or severe hypersensitivity to prior IMiD's such as
             thalidomide and lenalidomide.

          -  Patients requiring hemodialysis

          -  The patient is receiving medications that are:

               -  Exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4 (CYP3A4).

               -  Exclusively or primarily eliminated by Uridine 5'-diphospho
                  (UDP)-glucuronyltransferase 1A1 (UGT1A1).

               -  Substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a
                  narrow therapeutic window; or which are strong inhibitors of drug transporter
                  MDR1.

          -  Patients should have discontinued strong CYP1A2 inhibitors (e.g. ciprofloxacin and
             fluvoxamine) at least five half-lives before beginning study treatment.

          -  Inability to tolerate thromboprophylaxis (Required Concurrent Medications)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose (MTD) or maximum tested dose level of TEW-7197 given in combination with POM for the treatment of relapsed or RRMM
Time Frame:Up to 30 days after treatment ends (24 weeks + 30 days)
Safety Issue:
Description:the largest tested dose where multiple dose limiting toxicities are not observed

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 6 months after beginning treatment
Safety Issue:
Description:overall response is the complete response [CR] + very good partial response [VGPR] + partial response [PR] based on International Myeloma Working Group (IMWG) defined response criteria
Measure:Progression-free survival (PFS)
Time Frame:Up to 30 days after discontinuation of treatment
Safety Issue:
Description:Progression-free survival will be measured from study entry to progression or death of any cause, whichever comes first.
Measure:Progression-free survival at 6 months (PFS-6)
Time Frame:Up to 6 months after beginning treatment
Safety Issue:
Description:Number of patients who did not progress on treatment, at 6 months after beginning treatment
Measure:Duration of Response
Time Frame:Up to 6 months after beginning treatment
Safety Issue:
Description:The time from the first confirmed response to progression of disease. Responses include Complete Response (CR), Stringent CR, Very Good Partial Response, Partial Response, Minor Response, Stable disease. Responses based on International Myeloma Working Group (IMWG) defined response criteria
Measure:clinical benefit rate
Time Frame:Up to 6 months after beginning treatment
Safety Issue:
Description:clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on International Myeloma Working Group (IMWG) defined response criteria
Measure:Overall Survival
Time Frame:Up to 6 months after progression
Safety Issue:
Description:Overall survival for all will be measured from study entry to death from any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • TEW-7197
  • Pomalidomide

Last Updated

April 25, 2019