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A Study of GFH009 in Patients With Hematologic Malignancies

Primary Purpose

Hematologic Malignancies

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GFH009
GFH009
GFH009, venetoclax, azacitidine
Sponsored by
Genfleet Therapeutics (Shanghai) Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Acute myeloid leukemia, lymphoma, relapsed, refractory, CDK9 inhibitor, GFH009, venetoclax, azacitidine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  1. Patients with cytological or histologically confirmed relapsed or refractory hematologic malignancies (AML, CLL/SLL and lymphoma)
  2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN.

    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 × ULN.

  3. Amylase and lipase ≤1.5 × ULN
  4. Electrolytes and uric acid levels within normal limits (WNL) or correctable with medical intervention
  5. For women of childbearing potential, must consent to use two highly effective methods (i.e, total abstinence, placement of an intrauterine device) of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug; Men with a partner of childbearing potential, must consent to use two highly effective methods of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug.

Exclusion Criteria

  1. Patients with bulky disease who require cytoreductive therapy.
  2. Symptomatic central nervous system metastases or primary lymphoma such as primary CNS lymphoma, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS-directed therapy and are on a stable or decreasing dose of corticosteroids are eligible for study entry.
  3. Severe cardiovascular disease within 6 months of study entry, including any of the following:

    • Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), LVEF < 45% as determined by MUGA scan or echocardiogram (ECHO), (if just with historical occasional low LVEF but without any symptoms or relevant medical history, and the LVEF at screening is > 45%, the subject is eligible), or clinically significant arrythmia.
    • History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting).
    • QTcF ≥ 450 msec on screening ECG.
  4. Concurrent malignancy within 5 years (for AML patients, 2 years) prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, and superficial non-muscle invasive urothelial carcinoma (excluding T1 lesions and CIS).
  5. Chronic or active hepatitis B or hepatitis C virus infection.
  6. History of HIV infection.
  7. Concomitant medications that are strong CYP3A4 inhibitors and strong inducers within 7 days of first dose. Avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pomelos, star citrus fruits or St. John's wort within 7 days of first dose.
  8. Medications that are known to prolong the QT interval are prohibited on this study.

Sites / Locations

  • O'Neal Comprehensive Cancer Center, University of AlabamaRecruiting
  • Ochsner Clinic Foundation
  • Clinical Research Alliance, Inc.Recruiting
  • New York - Presbyterian Hospital
  • Bon Secours St. Francis Cancer CenterRecruiting
  • MD AndersonRecruiting
  • The First Affiliated Hospital of Bengbu Medical CollegeRecruiting
  • Anhui Provincial Hospital
  • Affiliated Cancer Hospital of Chongqing University
  • Cancer prevention and treatment center of Sun Yat sen UniversityRecruiting
  • Guangdong Provincial People's HospitalRecruiting
  • Affiliated Hospital of Hebei UniversityRecruiting
  • Henan Cancer HospitalRecruiting
  • The First Affiliated Hospital of Soochow UniversityRecruiting
  • The First Affiliated Hospital Of Nanchang UniversityRecruiting
  • Shengjing Hospital Affiliated to China Medical UniversityRecruiting
  • Linyi Cancer HospitalRecruiting
  • Blood disease hospital, Chinese Academy of Medical ScienceRecruiting
  • The Second Affiliated hospital of Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1. Dose escalation in patients with relapsed/refractory AML

Group 2. Dose escalation in patients with relapsed/refractory CLL/SLL or lymphoma

AML Patients relapsed/refractory to vene and who will be treated with GFH in combo with vene & aza

Arm Description

Group 3. Patients with relapsed/refractory AML who have relapsed on or are refractory to venetoclax-based regimens

Outcomes

Primary Outcome Measures

Safety and Tolerability of GFH009: Dose Limiting Toxicities (DLTs)
The incidence of DLTs
Safety and Tolerability of GFH009: adverse events (AEs)
The incidence and severity of all AEs

Secondary Outcome Measures

PK parameter AUC0-t
Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration)
PK parameter AUC0-∞
Area under the plasma concentration-time curve (from zero to infinity)
Efficacy: CR
Efficacy: DOR
Efficacy: PFS
Efficacy:OS
PK parameter Cmax
PK parameter Tmax
PK parameter Ctrough
PK parameter t½

Full Information

First Posted
September 28, 2020
Last Updated
August 29, 2023
Sponsor
Genfleet Therapeutics (Shanghai) Inc.
Collaborators
Sellas Life Sciences Group
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1. Study Identification

Unique Protocol Identification Number
NCT04588922
Brief Title
A Study of GFH009 in Patients With Hematologic Malignancies
Official Title
A Phase I/IIa, Open-Label Dose Escalation and Dose Expansion Study of Intravenous GFH009 Single Agent and in Combination With Venetoclax and Azacitidine in Patients With Relapsed/Refractory Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2021 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genfleet Therapeutics (Shanghai) Inc.
Collaborators
Sellas Life Sciences Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
GFH009 is a potent and highly selective CDK9 inhibitor. To assess the safety, tolerability, and antitumor activity of single agent GFH009, this study consists of two dose escalation groups in patients with relapsed/refractory acute myeloid leukemia (Group 1) and in patients with relapsed/refractory lymphomas (Group 2). The safety, tolerability, and antitumor activity of GFH009 in combination with venetoclax and azacitidine in patients with relapsed/refractory acute myeloid leukemia (AML) who have relapsed on or are refractory to venetoclax-based regimens will also be assessed (Group 3).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Acute myeloid leukemia, lymphoma, relapsed, refractory, CDK9 inhibitor, GFH009, venetoclax, azacitidine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
135 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1. Dose escalation in patients with relapsed/refractory AML
Arm Type
Experimental
Arm Title
Group 2. Dose escalation in patients with relapsed/refractory CLL/SLL or lymphoma
Arm Type
Experimental
Arm Title
AML Patients relapsed/refractory to vene and who will be treated with GFH in combo with vene & aza
Arm Type
Experimental
Arm Description
Group 3. Patients with relapsed/refractory AML who have relapsed on or are refractory to venetoclax-based regimens
Intervention Type
Drug
Intervention Name(s)
GFH009
Intervention Description
In the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. In the expansion part, patients will be assigned based on tumor type(s).
Intervention Type
Drug
Intervention Name(s)
GFH009
Intervention Description
In the dose escalation part, the dose levels will be escalated following the Bayesian optimal interval (BOIN) design. In the expansion part, patients will be assigned based on tumor type(s).
Intervention Type
Drug
Intervention Name(s)
GFH009, venetoclax, azacitidine
Intervention Description
Group 3. Patients with relapsed/refractory AML who have relapsed on or are refractory to venetoclax-based regimens
Primary Outcome Measure Information:
Title
Safety and Tolerability of GFH009: Dose Limiting Toxicities (DLTs)
Description
The incidence of DLTs
Time Frame
21 to 28 days
Title
Safety and Tolerability of GFH009: adverse events (AEs)
Description
The incidence and severity of all AEs
Time Frame
approximately 2 years
Secondary Outcome Measure Information:
Title
PK parameter AUC0-t
Description
Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration)
Time Frame
approximately 3 months
Title
PK parameter AUC0-∞
Description
Area under the plasma concentration-time curve (from zero to infinity)
Time Frame
approximately 3 months
Title
Efficacy: CR
Time Frame
2 years
Title
Efficacy: DOR
Time Frame
2 years
Title
Efficacy: PFS
Time Frame
2 years
Title
Efficacy:OS
Time Frame
2 years
Title
PK parameter Cmax
Time Frame
approximately 3 months
Title
PK parameter Tmax
Time Frame
approximately 3 months
Title
PK parameter Ctrough
Time Frame
approximately 3 months
Title
PK parameter t½
Time Frame
approximately 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients with cytological or histologically confirmed relapsed or refractory hematologic malignancies (AML, CLL/SLL and lymphoma) Lymphoma: At least one measurable or evaluable lesion as defined by the Lugano (2014) response criteria. Patients must have received at least 2 prior lines of systemic therapy. AML (only for Group 3): Patients relapsed on or refractory to venetoclax containing regimens. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN. • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 × ULN. Amylase ≤1.5 × ULN Electrolytes and uric acid level need to be stable judged by investigators for at least 3 days before the first dose of GFH009 (Medical intervention is permitted). For women of childbearing potential, must consent to use highly effective methods (i.e, total abstinence, placement of an intrauterine device) of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug, if enrolled in Groups 1 or 2, and 6 months if enrolled in Group 3. Men with a partner of childbearing potential, must consent to use two highly effective methods of contraception during GFH009 treatment and for an additional 90 days after the last administration of study drug. Exclusion Criteria Patients with bulky disease (≥ 10 cm) who require cytoreductive therapy. Symptomatic central nervous system metastases or primary lymphoma such as primary CNS lymphoma, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS-directed therapy and are on a stable or decreasing dose of corticosteroids are eligible for study entry. Severe cardiovascular disease within 6 months of study entry, including any of the following: Clinically significant heart disease such as congestive heart failure requiring treatment (NYHA class III or IV), LVEF < 50% as determined by MUGA scan or echocardiogram (ECHO), (if just with historical occasional low LVEF but without any symptoms or relevant medical history, and the LVEF at screening is > 50%, the subject is eligible), or clinically significant arrythmia. History/evidence of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting). Average QTcF ≥ 450 msec (males) or ≥ 470 msec (females) on screening ECG. Moderate or above regurgitation on echocardiogram Patients with prior treatment with cardiotoxic agents who have experienced drug induced cardiotoxicities during or after treatment, where cardiotoxic agents include but are not limited to: anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone); trastuzumab and trastuzumab based ADCs; tyrosine kinase inhibitors (sunitinib, imatinib); alkylating agents (cyclophosphamide). Patients with a baseline cardiac biomarker abnormality (CKMB/cTnI) will be excluded. Patients with hypereosinophilic syndrome defined as eosinophil counts in peripheral blood of ≥1,500/µ. Concurrent malignancy within 5 years (for AML patients, 2 years) prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, and superficial non-muscle invasive urothelial carcinoma (excluding T1 lesions and CIS). Active hepatitis B or hepatitis C virus infection. History of HIV infection or HIV positive at screening. Concomitant medications that are strong CYP3A4 inhibitors and strong inducers within 7 days of first dose. Avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pomelos, star citrus fruits or St. John's wort within 7 days of first dose. Medications that are known to prolong the QT interval that could not be stopped prior to study entry judged by investigator, except azole antifungal medications in AML patients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Young Li
Phone
+86 21 6882 1388
Email
yli@genfleet.com
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Info at Sellas
Phone
+1 646-200-5278
Email
clinicaltrialinfo@sellaslife.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dragan Cicic, MD
Organizational Affiliation
SELLAS Life Sciences Group, Inc.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Alan Zhu at GenFleet
Organizational Affiliation
Study Chair
Official's Role
Study Director
Facility Information:
Facility Name
O'Neal Comprehensive Cancer Center, University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Omer Jammy, MD
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Individual Site Status
Terminated
Facility Name
Clinical Research Alliance, Inc.
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James MD D'Olimpio, MD
Facility Name
New York - Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Terminated
Facility Name
Bon Secours St. Francis Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharif Khan, MD
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77091
Country
United States
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Bengbu Medical College
City
Bengbu
State/Province
Anhui
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
yanli yang
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
xuhan zhang
Facility Name
Affiliated Cancer Hospital of Chongqing University
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Withdrawn
Facility Name
Cancer prevention and treatment center of Sun Yat sen University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
zhiming li
Facility Name
Guangdong Provincial People's Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
xin du
Facility Name
Affiliated Hospital of Hebei University
City
Baoding
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
aimin zang
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
keshu zhou
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
suning chen
Facility Name
The First Affiliated Hospital Of Nanchang University
City
Nanchang
State/Province
Jiangxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
fei li
Facility Name
Shengjing Hospital Affiliated to China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
zhuogang liu
Facility Name
Linyi Cancer Hospital
City
Linyi
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
zhen wang
Facility Name
Blood disease hospital, Chinese Academy of Medical Science
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jianxiang wang
Facility Name
The Second Affiliated hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
wenbin qian

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study of GFH009 in Patients With Hematologic Malignancies

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