Clinical Trials /

A Study of CA-4948 in Patients With Relapsed or Refractory Hematologic Malignancies

NCT03328078

Description:

This is a multi-center, open-label trial of orally administered CA-4948 monotherapy in adult patients with Relapsed or Refractory Hematologic Malignancies. The trial will be conducted in 2 parts: an initial Dose Escalation Phase (Part A) of CA-4948 in patients with Relapsed or Refractory Hematologic Malignancies, and a Dose Expansion Phase (Part B) of CA-4948 in patients with selected RR hematologic malignancies (including NHL with and without myeloid differentiation primary response 88 (MYD88) mutations, and AML).

Related Conditions:
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CA-4948 in Patients With Relapsed or Refractory Hematologic Malignancies
  • Official Title: An Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients With Relapsed or Refractory Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CA-4948-101
  • NCT ID: NCT03328078

Conditions

  • Relapsed Hematologic Malignancy
  • Refractory Hematologic Malignancy

Interventions

DrugSynonymsArms
CA-4948CA-4948

Purpose

This is a multi-center, open-label trial of orally administered CA-4948 monotherapy in adult patients with Relapsed or Refractory Hematologic Malignancies. The trial will be conducted in 2 parts: an initial Dose Escalation Phase (Part A) of CA-4948 in patients with Relapsed or Refractory Hematologic Malignancies, and a Dose Expansion Phase (Part B) of CA-4948 in patients with selected RR hematologic malignancies (including NHL with and without myeloid differentiation primary response 88 (MYD88) mutations, and AML).

Trial Arms

NameTypeDescriptionInterventions
CA-4948ExperimentalPart A: Dose-level cohorts with up to 6 patients each will be used to define the Maximum Tolerated Dose (MTD) for CA-4948. Part B: The expansion phase of the study will be conducted in patients with Relapsed or Refractory Non-Hodgkin Lymphoma with and without MYD88 mutations and with Relapsed or Refractory Acute Myeloid Leukemia. Patients will be treated with CA-4948 at the Recommended Phase 2 Dose (RP2D) or the MTD (or highest dose tested if MTD is not reached).
  • CA-4948

Eligibility Criteria

        Inclusion Criteria:

          1. Males and females greater than or equal to 18 years of age

          2. Life expectancy of at least 3 months

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

          4. Diagnosis of histopathologically confirmed hematologic malignancies. For NHL:
             Confirmed B-cell NHL (as per the World Health Organization [WHO] 2016 classification
             including WM/LPL). For AML: Diagnosis of histopathologically confirmed AML (as per the
             World Health Organization [WHO] 2016 classification; Owen 2013) that is relapsed
             and/or refractory.

          5. Relapsed or refractory disease for which patients are ineligible for or have exhausted
             standard therapeutic options that would be considered standard of care

        Exclusion Criteria:

          1. Active central nervous system (CNS) involvement of their malignancy.

          2. Radiotherapy delivered to non-target lesions within one week prior to starting study
             treatment or delivered to target lesions that will be followed on the study (NOTE:
             prior sites of radiation will be recorded)

          3. History of allogeneic stem cell transplant for NHL

          4. Any prior anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy,
             etc., received within 14 days prior to start of CA-4948

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

               1. Doses ≤ 10 mg/day prednisolone or equivalent is allowed, provided that the
                  steroid dose has been stable or tapering for at least 14 days prior to the first
                  dose of CA-4948

               2. Inhaled, intranasal, intraarticular and topical steroids are permitted

          6. Use of any investigational agent within 28 days or 5 half-lives, whichever is shorter,
             prior to start of CA-4948

          7. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy,
             with the exception of alopecia, that has not resolved to Grade ≤ 1 within 7 days prior
             to start of CA-4948 unless approved by the Medical Monitor

          8. Known allergy or hypersensitivity to any component of the formulation of CA-4948 used
             in this study

          9. Diagnosis of acute promyelocytic leukemia (APL, M3) for AML

         10. Hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of CA-4948
             for AML

         11. Blast transformation of CML into AML
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle
Time Frame:12 months
Safety Issue:
Description:Toxicity will be graded and recorded according to the NCI CTCAE v4.03.

Secondary Outcome Measures

Measure:Pharmacokinetic (PK) profile of CA-4948 measured by AUC
Time Frame:24- 36 months
Safety Issue:
Description:Area Under the concentration-time curve (AUC)
Measure:Pharmacokinetic (PK) profile of CA-4948 measured by Cmax
Time Frame:24- 36 months
Safety Issue:
Description:Maximum plasma concentration (Cmax)
Measure:Pharmacokinetic (PK) profile of CA-4948 measured by Cmin
Time Frame:24- 36 months
Safety Issue:
Description:Trough plasma concentration (Cmin)
Measure:Pharmacokinetic (PK) profile of CA-4948 measured by Tmax
Time Frame:24- 36 months
Safety Issue:
Description:Time to maximum plasma concentration (Tmax)
Measure:Pharmacokinetic (PK) profile of CA-4948 measured by plasma terminal half-life
Time Frame:24- 36 months
Safety Issue:
Description:Plasma terminal elimination half-life (T 1/2)
Measure:Preliminary anti-cancer activity of oral CA-4948 in patients with RR NHL with and without MYD88 mutations and with RR AML
Time Frame:24- 36 months
Safety Issue:
Description:Assessed by Revised Response Criteria for Malignant Lymphoma (for NHL), by the consensus panel recommendations from the Sixth International Workshop on WM (for WM) and by the 2003 Revised IWG Criteria for AML (for AML).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Curis, Inc.

Trial Keywords

  • DLBCL
  • MCL
  • WM
  • LPL
  • MYD88
  • IRAK4
  • NHL
  • AML

Last Updated

January 17, 2019