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

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ClinicalTrials.gov Identifier: NCT03328078
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : January 21, 2019
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 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).

Condition or disease Intervention/treatment Phase
Relapsed Hematologic Malignancy Refractory Hematologic Malignancy Drug: CA-4948 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 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 Hematologic Malignancies
Actual Study Start Date : December 28, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

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 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).

Drug: CA-4948
CA-4948 (formulated for oral administration for QD or BID dosing)




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 oral CA-4948 in patients with RR NHL with and without MYD88 mutations and with RR AML [ Time Frame: 24- 36 months ]
    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).



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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 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

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
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Contact: Robert Martell, MD 617-503-6500 clinicaltrials@curis.com

Locations
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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, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Curis, Inc.

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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: January 21, 2019
Last Verified: January 2019

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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
NHL
AML

Additional relevant MeSH terms:
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Neoplasms