Clinical Trials /

Study to Evaluate the Efficacy and Safety of CUDC-907 in Patients With RR DLBCL, Including Patients With MYC Alterations

NCT02674750

Description:

This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of CUDC-907 in subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study to Evaluate the Efficacy and Safety of CUDC-907 With and Without <span class="go-doc-concept go-doc-intervention">Rituximab</span> in Patients With RR <span class="go-doc-concept go-doc-biomarker">MYC</span>-<span class="go-doc-concept go-doc-keyword">Altered</span> DLBCL

Title

  • Brief Title: Study to Evaluate the Efficacy and Safety of CUDC-907 With and Without Rituximab in Patients With RR MYC-Altered DLBCL
  • Official Title: Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of CUDC-907 With and Without Rituximab in Patients With Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT02674750

    ORG ID: CUDC-907-201

    Trial Conditions

    Relapsed and/or Refractory Diffuse Large B-cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    CUDC-907 CUDC-907, CUDC-907 + Rituximab
    Rituximab CUDC-907 + Rituximab

    Trial Purpose

    This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and
    safety of CUDC-907 monotherapy and R-907 (rituximab in combination with CUDC-907) in
    subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell
    Lymphoma (DLBCL).

    Detailed Description

    Patients with RR DLBCL will be screened for myelocytomatosis oncogene (MYC) alterations
    based on one of the following:

    - Recent pathology report (obtained within 1 year of study entry and/or within 1 line of
    prior therapy), and/or

    - Fresh tissue or archival tissue

    Note: central testing will be available to determine the eligibility of patients without
    access to local testing.

    Trial Arms

    Name Type Description Interventions
    CUDC-907 Experimental MYC + by FISH or by >=40% MYC by IHC CUDC-907
    CUDC-907 + Rituximab Experimental MYC + by FISH or by >=40% MYC by IHC CUDC-907, Rituximab

    Eligibility Criteria

    Inclusion Criteria:

    1. Age 18 years.

    2. One or two prior lines of therapy for the treatment of DLBCL. Prior stem cell
    transplant is allowed (salvage therapy, conditioning therapy and maintenance with
    transplant will be considered one prior treatment).

    3. Histopathologically confirmed diagnosis of RR DLBCL.

    Diagnosis of follicular lymphoma transformed to DLBCL (aka transformed DLBCL) is
    allowed.

    4. Histopathologically confirmed MYC gene-aberrant (MGA) or MYC protein expressor (MPE)
    status by archival tissue samples (collected within 1 year of study entry and/or
    within 1 line of prior therapy) or fresh tumor samples by one of the following:

    - Local or central laboratory (if local testing is not available) fluorescence in
    situ hybridization (FISH) results of MYC translocation, or

    - Local or central laboratory (if local testing is not available)
    immunohistochemical (IHC) results with expression of MYC 40%, and/or gene copy
    number gain by FISH.

    5. Confirmed availability of viable tissue (defined as archival tissue collected within
    1 year of study entry and/or within 1 line of prior therapy or fresh tumor samples)
    for central laboratory FISH and IHC testing and review prior to study dosing.

    Exclusion Criteria:

    1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.

    2. Known lymphomatous involvement of the central nervous system (CNS) unless deemed
    clear of malignant involvement by cytologic examination of cerebrospinal fluid.
    Subjects with known bone marrow involvement will require prior chemoprophylaxis per
    local standard to prevent CNS relapse.

    3. Known allergy or hypersensitivity to phosphatidylinositol 3 kinase (PI3K) inhibitors
    or any component of the formulations used in this study. Prior treatment with an
    histone deacetylase (HDAC) inhibitor is not allowed (whereas prior treatment with a
    PI3K inhibitor is allowed).

    4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine
    analogues) within 2 weeks of study entry.

    5. Radiotherapy delivered to target lesions that will be followed on the study (note:
    prior sites of radiation will be recorded).

    6. Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks
    prior to enrollment, whichever is longer.

    7. Current or planned glucocorticoid therapy, with the following exceptions:

    - Glucocorticoids to reduce the potential for infusion reactions to rituximab are
    allowed per institutional guidelines.

    - Doses 1 mg/kg/day prednisolone or equivalent glucocorticoid and inhalational
    therapies for conditions such as mild chronic obstructive pulmonary disease
    (COPD) and asthma are allowed.

    - Replacement dosing of steroids (defined as < 30 mg/day hydrocortisone or the
    equivalent) is allowed, provided that the steroid dose has been stable or
    tapering for at least 14 days prior to the first dose of CUDC-907.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    The efficacy of CUDC-907 in terms of progression-free survival (PFS)

    Secondary Outcome Measures

    The efficacy of CUDC-907 in terms of objective response rate (ORR)

    Trial Keywords

    BCL2

    BCL6

    MYC-Altered

    Double Hit (DH)

    Double Expressor (DE)