Clinical Trial - NCT03760666

A Study of Brequinar in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Recruiting

Sponsor: Clear Creek Bio, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03760666

Protocol Info

Short Description: Brequinar + DHODH in Acute Myelogenous Leukemia
Long Description: A Phase 1b/2a open-label, multi-center study to assess the safety, efficacy and pharmacokinetics of intrapatient dose-adjusted brequinar and inhibition of dihydroorotate dehydrogenase (DHODH) in adult subjects with acute myelogenous leukemia (AML)
MGH Status: Closed
Sponsor: Clear Creek Bio, Inc.
Disease Program: Leukemia

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

A Phase 1b/2a multi-center, open-label, non-randomized study to assess the safety, tolerability and efficacy of dose-adjusted brequinar in adult subjects with acute myeloid leukemia (AML).
Condition Title Intervention Phase
Acute Myeloid Leukemia Brequinar Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1b/2a Open-label, Multi-center Study to Assess the Safety, Efficacy and Pharmacokinetics of Intrapatient Dose-adjusted Brequinar and Inhibition of Dihydroorotate Dehydrogenase (DHODH) in Adult Subjects With AML

Primary Outcome Measures

Number of Participants with Treatment-Related Adverse Events [Time Frame: 12 months] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Response Rate (ORR) [Time Frame: 12 months] [Designated as safety issue: ]

Complete Remission (CR) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Complete Remission with Incomplete Hematologic Recovery (CRi) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Complete Remission with Partial Hematological Recovery (CRh) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Morphologic Leukemia Free State (MLFS) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Partial Remission (PR) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Event free survival (EFS) rate [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Duration of response [Time Frame: Up to approximately 12 months] [Designated as safety issue: ]

Brequinar Pharmacokinetics - Elimination Half-Life (T 1/2) [Time Frame: Up to 14 days after first dose.] [Designated as safety issue: ]

Brequinar Pharmacokinetics - AUC [Time Frame: Up to 14 days after first dose.] [Designated as safety issue: ]

DHO Plasma Level [Time Frame: Up to 14 days after first dose. Pre-dose at the beginning of each cycle (every 2 weeks for 3 months then every 4 weeks).] [Designated as safety issue: ]

Estimated Enrollment: 27
Study Start Date: November 2018
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: December 2019
Arms Assigned Interventions

Experimental:Brequinar

Brequinar dosed orally. Multiple doses.
Drug:Brequinar
Oral brequinar will be administered twice-weekly. After the first cohort of 6 subjects, dose adjustments can occur every 14-day cycle both at the intra-subject and the inter-cohort level depending on safety, efficacy, and biomarker levels.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

1. Willing and able to provide written informed consent for the trial.

2. Patients 18 years of age or older, with relapsed/refractory AML by World Health Organization classification who have exhausted available therapy.

3. ECOG Performance Status 0 to 2.

4. 12-lead ECG with no clinically unacceptable findings; adequate cardiac function/NYHA Class 0 to 2.

5. Adequate hepatic function (unless deemed to be related to underlying leukemia).

1. Direct bilirubin ≤ 2 x ULN

2. ALT ≤ 3 x ULN

3. AST ≤ 3 x ULN

6. Adequate renal function as documented by creatinine clearance ≥ 30 mL/min based on the Cockcroft-Gault equation.

7. In the absence of rapidly proliferative disease, the interval from prior leukemia-directed therapy to first dose of study drug will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. Hydrea is allowed up to 48 hours prior to the first dose for patients with rapidly proliferative disease.

8. The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of brequinar administration.

9. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.

Exclusion Criteria:

1. Patients in need of immediate leukapheresis.

2. Any concurrent uncontrolled clinically significant medical condition, laboratory abnormality, or psychiatric illness that could place the participant at unacceptable risk of study treatment.

3. QTc interval using Fridericia's formula (QTcF) ≥ 470 msec. Participants with a bundle branch block and prolonged QTc interval may be eligible after discussion with the medical monitor.

4. Pre-existing liver disease.

5. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions:

a. Intrathecal chemotherapy for prophylactic use or maintenance of controlled CNS leukemia.

6. Use of hydroxyurea for the purpose of leukemic cytoreduction may be allowed during the first 2 weeks of therapy if in the best interest of the participant and is approved by the medical monitor. Hydroxyurea can be used to treat leukocytosis if concurrent with and thought to be associated with presumed differentiation syndrome.

7. Presence of graft versus host disease (GVHD) which requires an equivalent dose of ≥ 0.5 mg/kg/day of prednisone or therapy beyond systemic corticosteroids (e.g. cyclosporine or other calcineurin inhibitors or other immunosuppressive agents used for GVHD).

8. Active cerebrospinal involvement of AML.

9. Diagnosis of acute promyelocytic leukemia (APL)

10. Clinically active hepatitis B (HBV) or hepatitis C (HCV) infection.

11. Severe gastrointestinal or metabolic condition that could interfere with the absorption of oral study medication.

12. Prior malignancy, unless it has not been active or has remained stable for at least 2 years. Participants with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if at the active surveillance stage, hormonal therapy has been initiated, or the malignancy has been surgically removed or treated with definitive radiotherapy.

13. Nursing women or women of childbearing potential (WOCBP) with a positive urine pregnancy test.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03760666

Locations

  • United States, California
    • City of Hope Duarte, California, United States, 91010
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth-Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Texas
    • The University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030

Sponsors and Collaborators

Clear Creek Bio, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03760666
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Clear Creek Bio, Inc.:

DHODH

Brequinar

Differentiation

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Brequinar

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019