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Trial record 5 of 520 for:    Neoplasms | Recruiting, Not yet recruiting, Available Studies | "Multiple Myeloma"

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

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ClinicalTrials.gov Identifier: NCT03143985
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Ehsan Malek, Case Comprehensive Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: TEW-7197 Drug: Pomalidomide Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of TEW-7197 in Combination With Pomalidomide (POM) in Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM)
Actual Study Start Date : July 21, 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: TEW-7197 + Pomalidomide

TEW-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.

Drug: TEW-7197
TEW-7197 is an inhibitor of protein serine/threonine kinase activity of TGF-β receptor type 1 (TGFBR1; ALK5). TEW-7197 inhibits the phosphorylation of the ALK5 substrates, Smad2 and Smad3, and the intracellular signaling of TGF-β. Dosing begins at 60mg by mouth, daily and may increase to 240mg by mouth daily in the absence of dose limiting toxicities
Other Names:
  • EW-7197
  • EW7197

Drug: Pomalidomide
POM, an analog of thalidomide, is an immunomodulatory agent with antineoplastic activity. Myeloma tumor cells exposed to POM, undergo growth arrest and increased apoptotic cell death. POM enhances T cell- and natural killer cell-mediated immunity and inhibit production of pro-inflammatory cytokines by monocytes. POM may be taken orally with water. Capsules should not be broken, chewed or opened. POM should be taken without food (at least 2 hours before or 2 hours after a meal). POM will be commercially available. POM will be taken by mouth at a dose of 4mg per day
Other Name: POM




Primary Outcome Measures :
  1. 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) ]
    the largest tested dose where multiple dose limiting toxicities are not observed


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 6 months after beginning treatment ]
    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

  2. Progression-free survival (PFS) [ Time Frame: Up to 30 days after discontinuation of treatment ]
    Progression-free survival will be measured from study entry to progression or death of any cause, whichever comes first.

  3. Progression-free survival at 6 months (PFS-6) [ Time Frame: Up to 6 months after beginning treatment ]
    Number of patients who did not progress on treatment, at 6 months after beginning treatment

  4. Duration of Response [ Time Frame: Up to 6 months after beginning treatment ]
    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

  5. clinical benefit rate [ Time Frame: Up to 6 months after beginning treatment ]
    clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on International Myeloma Working Group (IMWG) defined response criteria

  6. Overall Survival [ Time Frame: Up to 6 months after progression ]
    Overall survival for all will be measured from study entry to death from any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03143985


Contacts
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Contact: Ehsan Malek, MD 216-286-4441 Ehsan.Malek@Uhhospitals.org

Locations
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United States, Ohio
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Ehsan Malek, MD    216-844-0139    ehsan.malek@uhhospitals.org   
Principal Investigator: Ehsan Malek, MD         
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Withdrawn
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
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Principal Investigator: Ehsan Malek, MD University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

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Responsible Party: Ehsan Malek, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03143985     History of Changes
Other Study ID Numbers: CASE1A17
First Posted: May 8, 2017    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ehsan Malek, Case Comprehensive Cancer Center:
TEW-7197
Pomalidomide

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Pomalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents