Tagraxofusp and Decitabine for the Treatment of Chronic Myelomonocytic Leukemia
Primary Purpose
Chronic Myelomonocytic Leukemia, Chronic Myelomonocytic Leukemia-1, Chronic Myelomonocytic Leukemia-2
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Decitabine
Tagraxofusp-erzs
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelomonocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- The patient is >= 18 years old
Diagnosis of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) subtype chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO) and:
- Phase 1 dose escalation portion: CMML-1 or CMML-2 by WHO and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
Phase 2 dose expansion portion:
- Relapsed cohort (Cohort A): CMML-1 or CMML-2 by WHO and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
- Hypomethylating agents (HMA) naive cohort (Cohort B): CMML-1 or CMML-2 and intermediate-2 or high-risk International Prognostic Scoring System (IPSS)
- The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
- Left ventricular ejection fraction (LVEF) >= 50% as measured by multigated acquisition scan or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
- Serum creatinine =< 1.5 mg/dL (or =< 114 umol/L)
- Serum albumin >= 3.2 g/dL (or >= 32 g/L) in the absence of receipt of (IV) albumin within the previous 72 hours
- Total Bilirubin =< 1.5 mg/dL (or =< 26 umol/L)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal (ULN)
- Creatine kinase (CK) =< 2.5 times the ULN
- If a woman of child bearing potential (WOCBP), the patient has a negative serum or urine pregnancy test within 1 week prior to tagraxofusp treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines)
- The patient or legally authorized representative has signed informed consent prior to initiation of any study-specific procedures or treatment
- The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments
- The patient (either male or female) agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 2 months after the last tagraxofusp infusion
- Patient has an absolute neutrophil count (ANC) >= 0.5 x 10^9/L
Exclusion Criteria:
- Patient has persistent clinically significant toxicities grade >= 2 from previous chemotherapy not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
- Patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry
- Patient has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent
- Patient has previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product
- Patient has an active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that is requiring active therapy. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ- confined prostate cancer with no evidence of progressive disease
- Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
- Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study
- Patient has known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid
- Patient is receiving immunosuppressive therapy, with the exception of corticosteroids and tacrolimus, for treatment or prophylaxis of graft- versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study drug and there must be no evidence of grade >= 2 GVHD
- Patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness that would limit compliance with study requirements
- Patient is pregnant or breast feeding
- Patient has known human immunodeficiency virus (HIV)
- Patient has evidence of active or chronic hepatitis B or hepatitis C infection
- Patient is oxygen-dependent
- Patient has any medical condition that in the Investigator's opinion place the patient at an unacceptably high risk for toxicities
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (decitabine, tagraxofusp-erzs)
Arm Description
Patients receive decitabine IV over 60 minutes on days 1-5, and tagraxofusp-erzs IV over 15 minutes on days 1-3. Cycles of decitabine repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment with tagraxofusp-erzs repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Maximum tolerable dose (Phase I)
Incidence of dose limiting toxicities (Phase I)
Overall response (OR) (Phase II)
Will estimate the OR for the combination treatment along with the 95% credible interval. The association between OR rate and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Secondary Outcome Measures
Full Information
NCT ID
NCT05038592
First Posted
June 1, 2021
Last Updated
October 5, 2023
Sponsor
M.D. Anderson Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT05038592
Brief Title
Tagraxofusp and Decitabine for the Treatment of Chronic Myelomonocytic Leukemia
Official Title
Phase I/II Study of Tagraxofusp in Combination With Decitabine for Patients With Chronic Myelomonocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2022 (Actual)
Primary Completion Date
January 29, 2025 (Anticipated)
Study Completion Date
January 29, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
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/II trial studies the side effects, best dose, and effect of tagraxofusp and decitabine in treating patients with chronic myelomonocytic leukemia. Tagraxofusp consists of human interleukin 3 (IL3) linked to a toxic agent called DT388. IL3 attaches to IL3 receptor positive cancer cells in a targeted way and delivers DT388 to kill them. Chemotherapy drugs, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tagraxofusp and decitabine may help to control the disease in patients with chronic myelomonocytic leukemia.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety, tolerability and maximum tolerable dose (MTD) of tagraxofusp-erzs (tagraxofusp) in combination with decitabine.
II. To assess overall response (OR) rate to tagraxofusp in combination with decitabine.
SECONDARY OBJECTIVES:
I. To assess overall survival (OS), duration of response, relapse-free survival (RFS) and safety profile.
II. Correlative studies.
OUTLINE: This is a phase I, dose-escalation study of tagraxofusp-erzs followed by a phase II study.
Patients receive decitabine intravenously (IV) over 60 minutes on days 1-5, and tagraxofusp-erzs IV over 15 minutes on days 1-3. Cycles of decitabine repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment with tagraxofusp-erzs repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelomonocytic Leukemia, Chronic Myelomonocytic Leukemia-1, Chronic Myelomonocytic Leukemia-2, Myelodysplastic/Myeloproliferative Neoplasm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (decitabine, tagraxofusp-erzs)
Arm Type
Experimental
Arm Description
Patients receive decitabine IV over 60 minutes on days 1-5, and tagraxofusp-erzs IV over 15 minutes on days 1-3. Cycles of decitabine repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment with tagraxofusp-erzs repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Tagraxofusp-erzs
Other Intervention Name(s)
Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL-401, Tagraxofusp, Tagraxofusp ERZS
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerable dose (Phase I)
Time Frame
At end of cycle 1 (1 cycle = 28 days)
Title
Incidence of dose limiting toxicities (Phase I)
Time Frame
Up to end of cycle 1 (1 cycle = 28 days)
Title
Overall response (OR) (Phase II)
Description
Will estimate the OR for the combination treatment along with the 95% credible interval. The association between OR rate and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Time Frame
After 2 cycles of therapy (1 cycle = 28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient is >= 18 years old
Diagnosis of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) subtype chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO) and:
Phase 1 dose escalation portion: CMML-1 or CMML-2 by WHO and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
Phase 2 dose expansion portion:
Relapsed cohort (Cohort A): CMML-1 or CMML-2 by WHO and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
Hypomethylating agents (HMA) naive cohort (Cohort B): CMML-1 or CMML-2 and intermediate-2 or high-risk International Prognostic Scoring System (IPSS)
The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
Left ventricular ejection fraction (LVEF) >= 50% as measured by multigated acquisition scan or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
Serum creatinine =< 1.5 mg/dL (or =< 114 umol/L)
Serum albumin >= 3.2 g/dL (or >= 32 g/L) in the absence of receipt of (IV) albumin within the previous 72 hours
Total Bilirubin =< 1.5 mg/dL (or =< 26 umol/L)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal (ULN)
Creatine kinase (CK) =< 2.5 times the ULN
If a woman of child bearing potential (WOCBP), the patient has a negative serum or urine pregnancy test within 1 week prior to tagraxofusp treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines)
The patient or legally authorized representative has signed informed consent prior to initiation of any study-specific procedures or treatment
The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments
The patient (either male or female) agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 2 months after the last tagraxofusp infusion
Patient has an absolute neutrophil count (ANC) >= 0.5 x 10^9/L
Exclusion Criteria:
Patient has persistent clinically significant toxicities grade >= 2 from previous chemotherapy not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
Patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry
Patient has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent
Patient has previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product
Patient has an active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that is requiring active therapy. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ- confined prostate cancer with no evidence of progressive disease
Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study
Patient has known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid
Patient is receiving immunosuppressive therapy, with the exception of corticosteroids and tacrolimus, for treatment or prophylaxis of graft- versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study drug and there must be no evidence of grade >= 2 GVHD
Patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness that would limit compliance with study requirements
Patient is pregnant or breast feeding
Patient has known human immunodeficiency virus (HIV)
Patient has evidence of active or chronic hepatitis B or hepatitis C infection
Patient is oxygen-dependent
Patient has any medical condition that in the Investigator's opinion place the patient at an unacceptably high risk for toxicities
Hydroxyurea is permitted only in settings in which a patient had been receiving this agent prior to study entry; hydroxyurea may only be administered during Cycle 1. After Cycle 1, the use of hydroxyurea may be permitted in consultation with the Principal Investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guillermo Bravo, MD
Phone
713-794-3604
Email
ggarciam@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo M Bravo, MD
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, MD
Phone
713-794-3604
Email
ggarciam@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Guillermo M. Bravo, MD
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center
Learn more about this trial
Tagraxofusp and Decitabine for the Treatment of Chronic Myelomonocytic Leukemia
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