Clinical Trials /

A Phase I Study of Intravenous CHO-H01 in Patients With Refractory or Relapsed Follicular Lymphoma

NCT03221348

Description:

This is a single-arm open label trial to explore the tolerability, safety, PK, PD, and anti-tumor activity of various doses and schedules of CHO-H01 administered as monotherapy in subjects with follicular lymphoma. Groups of 6 subjects are planned for each cohort. The first 3 patients of each cohort will be evaluated to determine if it is appropriate to proceed with the additional 3 patients at that dose and schedule.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study of Intravenous CHO-H01 in Patients With Refractory or Relapsed Follicular Lymphoma
  • Official Title: A Phase I Open-label, Multiple Dose Study of CHO-H01 Administered Intravenously as a Single Agent to Subjects With Refractory or Relapsed Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: FOLHAT-001
  • NCT ID: NCT03221348

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
CHO-H01Open label treatment

Purpose

This is a single-arm open label trial to explore the tolerability, safety, PK, PD, and anti-tumor activity of various doses and schedules of CHO-H01 administered as monotherapy in subjects with follicular lymphoma. Groups of 6 subjects are planned for each cohort. The first 3 patients of each cohort will be evaluated to determine if it is appropriate to proceed with the additional 3 patients at that dose and schedule.

Detailed Description

      This is a single-arm open label trial to explore the tolerability, safety, PK, PD, and
      anti-tumor activity of various doses and schedules of CHO-H01 administered as monotherapy in
      subjects with follicular lymphoma. This is not an MTD study, but an evaluation of optimum
      biological activity.

      Groups of 6 subjects are planned for each cohort. The first 3 patients of each cohort will be
      evaluated to determine if it is appropriate to proceed with the additional 3 patients at that
      dose and schedule.

      Schema 1:

      1 mg/kg administered on D1 of Cycle 1 and D1 of subsequent 28 day cycles. Up to 6 cycles
      total are planned per subject.

      Schema 2-3 Details to be determined after analysis of first 3-6 patients treated on Schema 1.
      Doses may be either escalated or de-escalated, or modified for Cycles 2-6 relative to Cycle
      1. Schedules to be explored could include multiple doses with the first cycle: D1, D8 of 28
      day cycles and D1, D8, D15 of 28 days cycles. In no case will individual doses exceed
      10mg/kg.

      Decisions on whether to proceed with a schema and details of selected dose and schedule will
      be made during cohort data review meetings by a Clinical-Scientific Review Team (CSRT)
      comprised of the trial investigators and Medical/Clinical and Safety representatives from the
      Sponsor. Ad hoc members will be consulted as needed.
    

Trial Arms

NameTypeDescriptionInterventions
Open label treatmentExperimentalStudy drug (CHO-H01) administered on Day 1 of 28 day cycles up to 6 cycles total.
  • CHO-H01

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 18 years Histologically confirmed, measurable, CD20 positive Follicular B cell
             lymphoma with an indication for treatment for which there is no therapy of curative
             potential or of higher priority

          -  Life expectancy of greater than 1 year

          -  ECOG performance status of 0 to 1

          -  Last dose of prior anti-cancer therapy must be at least 56 days (or two half-lives for
             proteins, whichever is greater) prior to the first administration of the study drug
             (to satisfy the recognized requirement of at least 5 times the terminal half-life
             period for most drugs currently used, including most receptor tyrosine kinase (RTK)
             inhibitors).

          -  Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved
             to National Cancer Institute Common Terminology Criteria for Adverse Events
             (NCI-CTCAE) Grade 0 or 1.

          -  Subject must be willing and able to provide fresh tumor at Screening. Subjects will be
             asked to provide additional needle biopsy samples on C2D8 and C4D8. Archival tumor
             biopsy (i.e., tissue block or series of ≈10 slides) is requested if available, and
             should be provided during the Screening period.

          -  Local laboratories may be used for standard laboratory assessments:

        Adequate bone marrow function defined by: absolute neutrophil count (ANC) of ≥ 1.5 x 109/L,
        platelet count of ≥ 100.0 x 109/L, and hemoglobin ≥9.0 g/dL.

        Adequate hepatic function defined by: serum total bilirubin < 2 mg/dl (unless resulting
        from hemolysis), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x
        ULN (or ≤ 5 x ULN in subjects with liver metastases).

        Adequate renal function assessed by: serum creatinine within normal limits, or creatinine
        clearance (by Cockcroft Gault formula) ≥ 50 mL/min for subjects in whom serum creatinine
        may not adequately reflect renal function.

          -  Must have measurable disease as described in Lugano Revised Criteria for Response.
             This assessment is the responsibility of the investigator who may use local radiology
             to support this assessment.

          -  Willing and able to understand and sign an informed consent form and to comply with
             all aspects of the protocol.

          -  Willingness to use effective methods of contraception.

          -  Adequate T cell immune parameters - CD4 >500/mcL, CD8 > 250/mcL

          -  Bone marrow biopsy revealing adequate hematologic reserves

        Exclusion Criteria:

          -  Evidence of circulating tumor cells >500 cells/microliter of lymphocytes or equivalent

          -  History of allergic reactions to any component of the study drug

          -  Autoimmune disease (Exceptions: autoimmune thyroiditis)

          -  Concomitant use of systemic corticosteroids

          -  History of seizure disorder

          -  History of Central Nervous System (CNS) metastases or seizure disorder related to the
             malignancy.

          -  History of symptomatic congestive heart failure (CHF), unstable angina pectoris,
             unstable atrial fibrillation; cardiac arrhythmia

          -  Non-manageable electrolyte imbalances, including hypokalemia, hypocalcemia,
             hypomagnesemia, and hypomagnesemia, of Grade 2 or greater (NCI-CTCAE v. 4.0)

          -  Any uncontrolled intercurrent illness, infection, or other condition that could limit
             study compliance or interfere with assessments

          -  Pregnancy or breast feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse drug reactions
Time Frame:28 days
Safety Issue:
Description:Treatment-emergent adverse events and clinically significant laboratory values assessed for each subject and aggregated by type, frequency and severity by treatment cohort

Secondary Outcome Measures

Measure:Clinical response
Time Frame:8 weeks
Safety Issue:
Description:Lugano Revised Criteria for Response
Measure:Serum drug concentration
Time Frame:72 hours
Safety Issue:
Description:Serum drug concentration measured at different times following drug administration

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Cho Pharma Inc.

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