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Clinical Trial 19377

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03422627

Phase: Phase I/II
Principal Investigator: Pidala, Joseph

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Overview

Study Title

A Phase 1b/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 592 in Adult Subjects With Steroid Refractory Chronic Graft versus Host Disease

Summary

The purpose of Phase 1b is to evaluate the safety and tolerability of multiple ascending doses of efavaleukin alfa in participants with steroid refractory cGVHD. The purpose of Phase 2 is to evaluate the efficacy of efavaleukin alfa in participants with steroid refractory cGVHD as measured by ORR at 16 weeks according to the 2014 cGVHD NIH Consensus Criteria.

Objective

Primary: Phase 1b : To evaluate the safety and tolerability of multiple ascending doses of AMG 592 in subjects with steroid refractory cGVHD in order to estimate the MTD and establish the RP2D. Phase 2 :To evaluate the efficacy of AMG 592 in subjects with steroid refractory cGVHD as measured by the best overall response rate (ORR) during the study according to the 2014 cGVHD National Institutes of Health (NIH) Consensus Criteria. Secondary: Phase 1b :To evaluate the immunologic effects of AMG 592 including fold change from baseline in regulatory T cell (Treg), conventional T cell (Tcon), and NK cell numbers (cells/ìL) and the Treg/Tcon ratio. To characterize the PK profile following multiple ascending subcutaneous (SC) dose administrations of AMG 592. To evaluate the incidence of anti-AMG 592 antibody formation and cross-reactivity to native human interleukin-2 (IL-2). Phase 2: To evaluate the safety and tolerability of AMG 592 as measured by the occurrence of treatment-emergent adverse events. To evaluate ORR, as defined by 2014 cGVHD NIH Consensus Criteria at various timepoints in AMG 592- treated subjects. To evaluate failure free survival (FFS), defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy. To evaluate systemic steroid use. To evaluate changes in symptom burden as measured by the Lee Symptom Scale. To measure changes in quality of life as measured by Short Form Health Survey 36 version 2 (SF36v2) and Karnofsky performance status. To evaluate the PK of AMG 592. To evaluate the incidence of anti-AMG 592 antibody formation and cross reactivity to human IL-2.

Treatments

Therapies

Therapy (NOS)

Medications

AMG 592 ()

Inclusion Criteria

  • Participant is >18 years old at the time of signing the informed consent
  • Recipient of an allogeneic HSCT
  • Moderate to severe cGVHD at screening with involvement of at least 1 of the following organs at the screening and baseline visits: skin, mouth, eyes, GI tract, liver, lungs and joint and fascia.
  • No more than 3 previous treatments for cGVHD, excluding topical agents.
  • Participants may be receiving corticosteroid therapy provided that the dose is > Participants may be receiving other non-corticosteroid immunosuppresive therapies provided that the immunosuppressant dose is stable for at least 2 weeks prior to first dose of efavaleukin alfa.
  • Karnofsky performance status score > 50%.
  • Adequate bone marrow function indicated by ANC > 1.00 x 10^9/L and platelets > 50 x 10^9/L without growth factors or transfusions within the 4 weeks prior to starting efavaleukin alfa.

    • Exclusion Criteria

  • Concurrently receiving treatment with calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
  • Received ibrutinib or imatinib, bortezomib, entosplenib,ruxolitnib, or other JAK inhibitor or treatment with any investigational drug or device within 4 weeks prior to starting efavaleukin alfa.
  • Treatment with T-cell depleting, B-cell depleting or IL-2 signaling targeted medication (e.g., ATG, alemtuzumab, basiliximab, denileukin diftitox, IL-2, rituximab within 12 weeks prior to starting efavaleukin alfa.
  • Treatment with T regulatory cell expanding therapies (i.e., ECP, PUVA, UVB, adoptively transferred T regulatory cells) within 4 weeks prior to starting dose of efavaleukin alfa.
  • Donor lymphocyte infusion within 12 weeks prior to starting dose of efavaleukin alfa.
  • Active morphologic relapse/progression of hematologic malignancy post transplantation.
  • History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
  • Active infection requiring treatment with IV antibiotics or hospitalized for treatment of an active infection in 4 weeks prior to starting dose of efavaleukin alfa.
  • History of active tuberculosis.
  • Hepatitis B and Hepatitis C.
  • HIV-positive.
  • Phase 1b: has a positive drug or alcohol urine test at screening visit.
  • Phase 1b: is unable to avoid alcohol or tobacco consumption for the duration of the study.
  • Other exclusions apply

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