Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents
Primary Purpose
Refractory Chronic Myelomonocytic Leukemia, Refractory Myelodysplastic Syndrome
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fostamatinib
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Chronic Myelomonocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 years as MDS is a very rare disease in the pediatric setting
- Diagnosis of MDS or CMML according to World Health Organization (WHO) and very low, low or intermediate risk by Revised International Prognostic Scoring System (IPSS-R) (with IPSS-R score of =< 3.5)
- Patients need to have not responded to prior therapy with hypomethylating agents (HMAs). These could include azacitidine, decitabine, SGI-110, ASTX727. Patients will need to have received at least 4 cycles of HMA. Patients with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Patients with MDS with isolated del(5q) must have received prior therapy with lenalidomide
Cytopenias, in the form of anemia and thrombocytopenia, as follows:
- Hemoglobin < 10 g/dL OR
- Platelets < 75 x10^9/L OR
- Transfusion dependency, defined as the receipt of any red blood cell or platelet transfusions within at least 28 days prior to the start of study treatment
- Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
- Total bilirubin < 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x ULN
- Serum creatinine clearance > 30 mL/min and no end/stage renal disease (using Cockcroft-Gault)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Hydroxyurea for control of leukocytosis is allowed at any time prior to or during study if considered to be in the best interest of the patient
- Both females of childbearing potential and males with female partners of childbearing potential must agree to use contraception during the study period and for at least one month after the last dose
Exclusion Criteria:
- No prior therapy for MDS or CMML
- Uncontrolled infection not adequately responding to appropriate antibiotics
- Absolute neutrophil count (ANC) < 0.5 x 10^9 k/uL
- Uncontrolled or poorly controlled hypertension, defined as systolic blood pressure >= 135 mmHg or diastolic blood pressure >= 85 mmHg, whether or not the subject is receiving anti-hypertensive treatment
- Female patients who are pregnant or lactating
- Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months
- Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta human chorionic gonadotropin [HCG]) pregnancy test at screening
- History of an active malignancy within the past 2 years prior to study entry, with the exception of: a. Adequately treated in situ carcinoma of the cervix uteri b. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin or any other malignancy with a life expectancy of more than 2 years
- Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
- Evidence of graft versus host disease or prior allo-stem cell transplantation within 6 months of Cycle 1 Day 1 or receiving immunosuppressants following a stem-cell procedure
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (fostamatinib)
Arm Description
Patients receive fostamatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles (week 24) in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
The PI doesnt wish to add any Outcome Measures this will be add at the time of results
Secondary Outcome Measures
Full Information
NCT ID
NCT05030675
First Posted
August 9, 2021
Last Updated
October 6, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT05030675
Brief Title
Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents
Official Title
Phase I Open-Label Study of Fostamatinib, a SYK Inhibitor, in Patients With Lower-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 13, 2021 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase I trial is to find out the best dose, possible benefits and/or side effects of fostamatinib in treating patients with lower-risk myelodysplastic syndromes or chronic myelomonocytic leukemia who have failed therapy with hypomethylating agents. Fostamatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVE:
I. To assess the safety and tolerability of different doses of fostamatinib in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) as the measure of adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities on fostamatinib treatment and frequency of discontinuation or interruptions of fostamatinib due to fostamatinib related AEs.
SECONDARY OBJECTIVES:
I. To assess overall survival (OS), duration of response, relapse-free survival (RFS).
II. To assess overall response (OR) rate to different dose schedules of fostamatinib in patients with MDS and CMML following International Working Group (IWG) 2006 response criteria.
III. Hematological response at the end of 2 cycles for each dose level. IV. Frequency of dose escalation of fostamatinib to a dose greater than 100 mg twice daily (BID).
V. Frequency of platelet transfusion independence. VI. Frequency of red blood cell (RBC) transfusion independence for > 8 weeks. VII. Endpoints related to correlative studies.
OUTLINE: This is a dose-escalation study.
Patients receive fostamatinib orally (PO) BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles (week 24) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 6 months thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Chronic Myelomonocytic Leukemia, Refractory Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (fostamatinib)
Arm Type
Experimental
Arm Description
Patients receive fostamatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles (week 24) in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Other Intervention Name(s)
R-935788 Free Acid, R788 Free Acid
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
The PI doesnt wish to add any Outcome Measures this will be add at the time of results
Time Frame
through study completion, an average of 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >= 18 years as MDS is a very rare disease in the pediatric setting
Diagnosis of MDS or CMML according to World Health Organization (WHO) and very low, low or intermediate risk by Revised International Prognostic Scoring System (IPSS-R) (with IPSS-R score of =< 3.5)
Patients need to have not responded to prior therapy with hypomethylating agents (HMAs). These could include azacitidine, decitabine, SGI-110, ASTX727. Patients will need to have received at least 4 cycles of HMA. Patients with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Patients with MDS with isolated del(5q) must have received prior therapy with lenalidomide
Cytopenias, in the form of anemia and thrombocytopenia, as follows:
Hemoglobin < 10 g/dL OR
Platelets < 75 x10^9/L OR
Transfusion dependency, defined as the receipt of any red blood cell or platelet transfusions within at least 28 days prior to the start of study treatment
Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
Total bilirubin < 2 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x ULN
Serum creatinine clearance > 30 mL/min and no end/stage renal disease (using Cockcroft-Gault)
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Hydroxyurea for control of leukocytosis is allowed at any time prior to or during study if considered to be in the best interest of the patient
Both females of childbearing potential and males with female partners of childbearing potential must agree to use contraception during the study period and for at least one month after the last dose
Exclusion Criteria:
No prior therapy for MDS or CMML
Uncontrolled infection not adequately responding to appropriate antibiotics
Absolute neutrophil count (ANC) < 0.5 x 10^9 k/uL
Uncontrolled or poorly controlled hypertension, defined as systolic blood pressure >= 135 mmHg or diastolic blood pressure >= 85 mmHg, whether or not the subject is receiving anti-hypertensive treatment
Female patients who are pregnant or lactating
Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months
Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta human chorionic gonadotropin [HCG]) pregnancy test at screening
History of an active malignancy within the past 2 years prior to study entry, with the exception of: a. Adequately treated in situ carcinoma of the cervix uteri b. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin or any other malignancy with a life expectancy of more than 2 years
Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
Evidence of graft versus host disease or prior allo-stem cell transplantation within 6 months of Cycle 1 Day 1 or receiving immunosuppressants following a stem-cell procedure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo M Bravo
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillermo M. Bravo
Phone
713-794-3604
Email
gmontalban1@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Guillermo M. Bravo
12. IPD Sharing Statement
Learn more about this trial
Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents
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