Tagraxofusp for Pediatric Blood Cancers
This study is testing a drug called Tagraxofusp in children and young adults (ages 1 to 21) who have blood cancers (hematologic malignancies) that have come back or are not responding to treatment. These cancers include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Tagraxofusp works by targeting a specific protein called CD123 on cancer cells. The main goal of this study is to see how safe Tagraxofusp is when given with other chemotherapy drugs like Fludarabine, Cytarabine, Dexamethasone, and Vincristine. Researchers will be looking for any serious side effects during the first cycle of treatment.
- Study design
- This is an interventional study planning to enroll 54 participants. The phase of the study is not specified.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Researchers will measure the occurrence of dose-limiting toxicity during the first cycle of therapy, which is 21 days for Part 1 and 28 days for Part 2.
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NCT05476770
Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies
Recruiting
PHASE1Ages 1–21InterventionalTreatmentTherapeutic Advances in Childhood Leukemia ConsortiumInvestigator-initiated
~54 participants
Updated 2024-12-06 on ClinicalTrials.gov
What's tested:TagraxofuspFludarabineCytarabineDexamethasoneVincristineAzacitidine
At a glance
Recruiting sites
15 of 31 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Occurrence of dose limiting toxicity (DLT) during cycle 1 of therapy
Measured over At the end of Cycle 1 (21 days for Part 1, and 28 days for Part 2)
Conditions
Where it's being run
31 sites across 23 statesCalifornia3
Ohio3
Texas3
Maryland2
New York2
Colorado1
District of Columbia1
Florida1
Study leadership
- Adam Lamble, MD · STUDY_CHAIR · Seattle Children's Hospital
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment.
Relapsed and/or refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma).
Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution.
Second or greater relapse; or
Refractory after 2 or more chemotherapy cycles; or
First relapse after primary chemotherapy-refractory disease; or
BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
First or greater relapse; or
Refractory after 2 or more chemotherapy cycles; or
BPDCN in first relapse or refractory after 1 or more chemotherapy cycles
\>5% blasts in the bone marrow aspirate or biopsy by morphology or flow cytometry
Patients with 1% - 5% blasts are eligible for Part 2, Cohort C (only), if A single bone marrow sample with flow cytometry and at least one other test (e.g. karyotype, FISH, PCR, or NGS) shows ≥ 1% leukemic blasts and/or flow cytometry demonstrates a stable or rising level of disease on two serial bone marrows.
Histologic verification of relapse
Measurable disease documented by radiographic criteria or bone marrow
Patients in Part 1 may have sites of non-CNS extramedullary disease, but no CNS disease. Patients in Part 2 may have CNS disease and/or other non-CNS extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
Patients with Down syndrome are eligible to participate in Part 1 only.
Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age (See Appendix I for Performance Scales). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
"Maintenance-style" therapy: therapy including vincristine (dosed a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed a maximum of one-time weekly), intrathecal therapy (dosed a maximum of one-time weekly) and/or dexamethasone (dosed at ≤3 mg/m2/dose twice daily) or prednisone (dosed at ≤20 mg/m2/dose twice daily) can be continued for up to 24 hours prior to entering the study.
Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
Monoclonal antibodies: Maximum of 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody.
Immunotherapy: At least 30 days from last infusion of chimeric antigen receptor T cell (CART) therapy or tumor vaccine.
Radiation Therapy (XRT):
Patients that have received other non-tagraxofusp CD123 targeting agents are eligible. Patients that have previously received tagraxofusp are not eligible.
Patients should not be known to be refractory to red blood cell or platelet transfusions.
Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be ≥20,000/mm3 to initiate therapy (may receive platelet transfusions).
Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below:
1 to \< 2 years old - Male: 0.6, Female: 0.6
2 to \< 6 years old - Male:0.8, Female: 0.8
6 to \< 10 years old - Male: 1, Female: 1
10 to \< 13 years old - Male: 1.2, Female: 1.2
13 to \< 16 years old - Male: 1.5, Female: 1.4
≥ 16 years old - Male: 1.7, Female: 1.4
Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x institutional upper limit of normal for age
SGPT (ALT) and SGOT (AST) must be less than 3x institutional upper limit of normal.
Serum albumin ≥3.2 g/dL (albumin infusion independent).
Shortening fraction of ≥27% by echocardiogram, or
Ejection fraction of ≥ 50% by gated radionuclide study/echocardiogram.
Pulse oximetry \> 94% on room air (\> 90% if at high altitude)
No evidence of dyspnea at rest and no exercise intolerance.
Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
Female patients with infants must agree not to breastfeed their infants while on this study.
Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 12 weeks after the last dose of tagraxofusp.
Anti-GVHD or agents to prevent organ rejection post-transplant - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 4 weeks must have elapsed after the last dose of GVHD meds.
Positive blood culture within 48 hours of study enrollment;
Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
A positive fungal culture within 30 days of study enrollment.
Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed.
Patients will be excluded if they have a known allergy to any of the drugs used in the study.
Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
Exclusion
Patients with CNS disease are not eligible for Part 1.
Patients with isolated CNS disease are not eligible for Part 1 or Part 2.
Patients with isolated non-CNS disease are eligible for Part 1 and Part 2.
Corticosteroids - Patients receiving corticosteroids for disease control who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
Investigational Drugs - Patients who are currently receiving another investigational drug are not eligible. The definition of "investigational" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia)
What this trial measures
- Occurrence of dose limiting toxicity (DLT) during cycle 1 of therapyAt the end of Cycle 1 (21 days for Part 1, and 28 days for Part 2)
The incidence of dose limiting toxicity (DLT) will be measured at different dose levels.