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A Study of CA-4948 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT03328078
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Curis, Inc.

Brief Summary:
This is a multi-center, open-label trial of orally administered CA-4948 monotherapy in adult patients with Relapsed or Refractory NHL. The trial will be conducted in 2 parts: an initial Dose Escalation Phase (Part A) of CA-4948 in patients with Relapsed or Refractory Non-Hodgkin Lymphoma, (RR NHL) and a Dose Expansion Phase (Part B) of CA-4948 in patients with RR NHL with and without myeloid differentiation primary response 88 (MYD88) mutations. During Part B, patients will be enrolled regardless of MYD88 mutation status.

Condition or disease Intervention/treatment Phase
Relapsed Non Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Drug: CA-4948 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Non-Hodgkin Lymphoma
Actual Study Start Date : December 28, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: CA-4948

Part 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. 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).

Drug: CA-4948
CA-4948




Primary Outcome Measures :
  1. The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle [ Time Frame: 12 months ]
    Toxicity will be graded and recorded according to the NCI CTCAE v4.03.

  2. Maximum tolerated dose (MTD) of CA-4948 measured by dose-limiting toxicities (DLTs) [ Time Frame: 12 months ]
    MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (<33%) experience a dose limiting toxicity

  3. Recommended Phase 2 Dose (RP2D) of CA-4948 based on overall tolerability data [ Time Frame: 12 months ]
    RP2D selected based on overall tolerability data from all patients treated at different dose levels and will not exceed the MTD.


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) profile of CA-4948 measured by AUC [ Time Frame: 24- 36 months ]
    Area Under the concentration-time curve (AUC)

  2. Pharmacokinetic (PK) profile of CA-4948 measured by Cmax [ Time Frame: 24- 36 months ]
    Maximum plasma concentration (Cmax)

  3. Pharmacokinetic (PK) profile of CA-4948 measured by Cmin [ Time Frame: 24- 36 months ]
    Trough plasma concentration (Cmin)

  4. Pharmacokinetic (PK) profile of CA-4948 measured by Tmax [ Time Frame: 24- 36 months ]
    Time to maximum plasma concentration (Tmax)

  5. Pharmacokinetic (PK) profile of CA-4948 measured by plasma terminal half-life [ Time Frame: 24- 36 months ]
    Plasma terminal elimination half-life (T 1/2)

  6. Preliminary anti-cancer activity of CA-4948 based on Revised Response Criteria for Malignant Lymphoma or the consensus panel recommendations from the Sixth International Workshop on WM [ Time Frame: 24- 36 months ]
    Non-Hodgkin Lymphoma (NHL) patients other than Waldenström macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL) patients assessed by Revised Response Criteria for Malignant Lymphoma; WM/LPL patients assessed by the consensus panel recommendations from the Sixth International Workshop on WM



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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:

  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 B-cell NHL (as per the World Health Organization [WHO] 2016 classification) including WM/LPL.
  5. Relapsed or refractory disease (as defined below) 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
  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 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

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): NCT03328078


Contacts
Contact: Hongwei Wang, MD 617-503-6500 clinicaltrials@curis.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Nebraska
Fred and Pamela Buffett Cancer Center Recruiting
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Curis, Inc.

Responsible Party: Curis, Inc.
ClinicalTrials.gov Identifier: NCT03328078     History of Changes
Other Study ID Numbers: CA-4948-101
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: January 2018

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

Keywords provided by Curis, Inc.:
DLBCL
MCL
WM
LPL
MYD88
IRAK4

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases