Tagraxofusp and Decitabine for the Treatment of Chronic Myelomonocytic Leukemia

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT05038592
Collaborator
(none)
64
Enrollment
1
Location
1
Arm
10.9
Anticipated Duration (Months)
5.9
Patients Per Site Per Month

Study Details

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:
  1. To determine the safety, tolerability and maximum tolerable dose (MTD) of tagraxofusp-erzs (tagraxofusp) in combination with decitabine.

  2. To assess overall response (OR) rate to tagraxofusp in combination with decitabine.

SECONDARY OBJECTIVES:
  1. To assess overall survival (OS), duration of response, relapse-free survival (RFS) and safety profile.

  2. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
64 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Study of Tagraxofusp in Combination With Decitabine for Patients With Chronic Myelomonocytic Leukemia
Actual Study Start Date :
Mar 4, 2022
Anticipated Primary Completion Date :
Jan 29, 2023
Anticipated Study Completion Date :
Jan 29, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (decitabine, tagraxofusp-erzs)

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.

Drug: Decitabine
Given IV
Other Names:
  • 5-Aza-2''-deoxycytidine
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
  • Biological: Tagraxofusp-erzs
    Given IV
    Other Names:
  • 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
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum tolerable dose (Phase I) [At end of cycle 1 (1 cycle = 28 days)]

    2. Incidence of dose limiting toxicities (Phase I) [Up to end of cycle 1 (1 cycle = 28 days)]

    3. Overall response (OR) (Phase II) [After 2 cycles of therapy (1 cycle = 28 days)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1M D Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center

    Investigators

    • Principal Investigator: Guillermo M Bravo, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT05038592
    Other Study ID Numbers:
    • 2020-0895
    • NCI-2021-04293
    • 2020-0895
    First Posted:
    Sep 9, 2021
    Last Update Posted:
    Mar 7, 2022
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 7, 2022