Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies

Part of paid clinical trials in Los Angeles, California.

Sponsor
Therapeutic Advances in Childhood Leukemia Consortium
Study ID
NCT05476770
Phase
PHASE1
Status
Recruiting
Apply to this trial

Conditions

  • ALL
  • AML
  • Acute Undifferentiated Leukemia
  • BPDCN
  • Hematologic Malignancy
  • Hodgkin Lymphoma
  • Lymphoblastic Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, T-Cell
  • MDS
  • Mixed Phenotype Acute Leukemia

Eligibility Criteria

Sex
ALL
Age
1 Year - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Tagraxofusp — DRUG
    Dose will be assigned at study entry. Give IV over 15 minutes.
  • Fludarabine — DRUG
    30 mg/m\^2 will be given IV over 30 minutes on days 1-5. Infusion will start 30 minutes after start of tagraxofusp on days 4 and 5.
  • Cytarabine — DRUG
    2000 mg/m2 intravenously will be given daily over 1-3 hours for 5 days on days 1 through 5. Infusion will begin 4 hours after start of fludarabine. Because of an increased risk of neurotoxicity, it is recommended that IT cytarabine be separated from high dose IV cytarabine administration by at least 24 hours on C1D1.
  • Dexamethasone — DRUG
    * 20 mg/m2/day divided BID (max 40 mg/day) given orally on days 1 through 5 and 15 through 19. The two doses should be separated by at least 8 hours. * Any oral formulation of dexamethasone is acceptable. * IV may be given if oral formulation is not tolerated
  • Vincristine — DRUG
    * 1.5 mg/m2 (maximum dose 2 mg) given intravenously as an IV push over 1-5 minutes or infusion via minibag as per institutional policy on days 1, 8, 15, and 22. * Infusion will start 30 minutes after start of tagraxofusp on day 8.
  • Azacitidine — DRUG
    * 75 mg/m2 subcutaneously or intravenously will be given daily over 15 minutes for 5 days on days 1 through 5. * Azacitidine will be given 30-60 minutes before beginning the tagraxofusp infusion.
  • Methotrexate — DRUG
    Give intrathecally: * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients ≥9 years of age
  • Cytarabine IT — DRUG
    Give intrathecally: * 30 mg for patients age 1-1.99 * 50 mg for patients age 2-2.99 * 70 mg for patients ≥3 years of age If given as part of Triple IT Therapy: AML Patients: Age 1-1.99 - 24 mg Age 2-2.99 - 30 mg Age ≥3 years of age - 36 mg AML Patients: Age 1-1.99 - 16 mg Age 2-2.99 - 20 mg Age 3-8.99 - 24 mg Age ≥9 years of age - 30 mg
  • Hydrocortisone — DRUG
    Given intrathecally. AML Patients: Age 1-1.99 - 16 mg Age 2-2.99 - 20 mg Age ≥3 years of age - 24 mg AML Patients: Age 1-1.99 - 8 mg Age 2-2.99 - 10 mg Age 3-8.99 - 12 mg Age ≥9 years of age - 15 mg

Study Details

Tagraxofusp is a protein-drug conjugate consisting of a diphtheria toxin redirected to target CD123 has been approved for treatment in pediatric and adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This trial aims to examine the safety of this novel agent in pediatric patients with relapsed/refractory hematologic malignancies. The mechanism by which tagraxofusp kills cells is distinct from that of conventional chemotherapy. Tagraxofusp directly targets CD123 that is present on tumor cells, but is expressed at lower or levels or absent on normal hematopoietic stem cells. Tagraxofusp also utilizes a payload that is not cell cycle dependent, making it effective against both highly proliferative tumor cells and also quiescent tumor cells. The rationale for clinical development of tagraxofusp for pediatric patients with hematologic malignancies is based on the ubiquitous and high expression of CD123 on many of these diseases, as well as the highly potent preclinical activity and robust clinical responsiveness in adults observed to date. This trial includes two parts: a monotherapy phase and a combination chemotherapy phase. This design will provide further monotherapy safety data and confirm the FDA approved pediatric dose, as well as provide safety data when combined with chemotherapy. The goal of this study is to improve survival rates in children and young adults with relapsed hematological malignancies, determine the recommended phase 2 dose (RP2D) of tagraxofusp given alone and in combination with chemotherapy, as well as to describe the toxicities, pharmacokinetics, and pharmacodynamic properties of tagraxofusp in pediatric patients. About 54 children and young adults will participate in this study. Patients with Down syndrome will be included in part 1 of the study.

Key Dates

Start date
Nov 11, 2022
Status verified
Dec 2024
Primary completion
Nov 11, 2025
Completion
Nov 11, 2027

Study Design

Enrollment
54 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1
    Tagraxofusp -Days 1-5 IT Therapy (may include methotrexate, cytarabine, or triple IT) * Day 1 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator
  • Experimental: Part 2 - Cohort A
    Tagraxofsup -Days 4-8 Fludarabine -Days 1-5 Cytarabine -Days 1-5 IT Therapy (may include methotrexate, cytarabine, or triple IT) CNS1 IT Therapy * Day 1 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator CNS2/3 IT Therapy * Days 1, 8, 15, and 22 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator
  • Experimental: Part 2 - Cohort B
    Tagraxofsup -Days 8-12 Dexamethasone -Days 1-5 Vincristine -Days 1, 8, 15, and 22 IT Therapy (may include methotrexate, cytarabine, or triple IT) CNS1 IT Therapy * Day 1 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator CNS2/3 IT Therapy * Days 1, 8, 15, and 22 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator
  • Experimental: Part 2 - Cohort C
    Tagraxofsup -Days 1-5 Azacitidine -Days 1-5 IT Therapy (may include methotrexate, cytarabine, or triple IT) CNS1 IT Therapy * Day 1 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator CNS2/3 IT Therapy * Days 1, 8, 15, and 22 * Patients may receive additional IT therapy with their end-of-cycle disease re-evaluation at the discretion of the treating investigator

Primary Outcome Measure

Occurrence of dose limiting toxicity (DLT) during cycle 1 of therapy [ Time Frame: At the end of Cycle 1 (21 days for Part 1, and 28 days for Part 2) ]

Central Contacts

Locations (29)

FacilityCityStateZIPSite coordinators
Children's Hospital Los AngelesLos AngelesCalifornia90027
Alan Wayne, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital Orange CountyOrangeCalifornia92868
Van Thu Huynh, MD (PRINCIPAL_INVESTIGATOR)
UCSF School of MedicineSan FranciscoCalifornia94143-0106
Michelle Hermiston, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital ColoradoDenverColorado80045
Margaret Macy, MD (PRINCIPAL_INVESTIGATOR)
Children's National Medical CenterWashington D.C.District of Columbia20010
Reuven Schore, MD (PRINCIPAL_INVESTIGATOR)
University of MiamiMiamiFlorida33136
Julio Barredo, MD
Children's Healthcare of Atlanta, Emory UniversityAtlantaGeorgia30322
Melinda Pauly, MD (PRINCIPAL_INVESTIGATOR)
Ann & Robert H. Lurie Children's Hospital of ChicagoChicagoIllinois60611
Jenna Rossoff, MD (PRINCIPAL_INVESTIGATOR)
Riley Hospital for ChildrenIndianapolisIndiana46202
Sandeep Batra, MD
Johns Hopkins UniversityBaltimoreMaryland21231
Pat Brown, MD (PRINCIPAL_INVESTIGATOR)
National Cancer Institute, Pediatric Oncology BranchBethesdaMaryland20892
Nirali Shah, MD (PRINCIPAL_INVESTIGATOR)
Dana-Farber Cancer InstituteBostonMassachusetts02215
Andrew Place, MD (PRINCIPAL_INVESTIGATOR)
C.S. Mott Children's HospitalAnn ArborMichigan48109-0914
Rajen Mody, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital and Clinics of MinnesotaMinneapolisMinnesota55404
Nathan Gossai, MD
Nathan Gossai, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital New York-PresbyterianNew YorkNew York10032
Nobuko Hijiya, MD (PRINCIPAL_INVESTIGATOR)
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065
Maria Sulis, MD, MS
Carolina-Levine Children's HospitalCharlotteNorth Carolina28204
Joel Kaplan, MD (PRINCIPAL_INVESTIGATOR)
Cincinnati Children's Hospital Medical CenterCincinnatiOhio45229
Robin Norris, MD
Rainbow BabiesClevelandOhio44106
Rachel Egler, MD (PRINCIPAL_INVESTIGATOR)
Nationwide Children's HospitalColumbusOhio43205
Susan Vear-Colace, MD (PRINCIPAL_INVESTIGATOR)
Oregon Health & Science UniversityPortlandOregon97239
Bill Chang, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19104
Sue Rheingold, MD (PRINCIPAL_INVESTIGATOR)
St. Jude Children's Research HospitalMemphisTennessee38105
Jeffrey Rubnitz, MD
University of Texas, SouthwesternDallasTexas75235
Tamra Slone, MD
Cook Children's HospitalFort WorthTexas76104
Kenneth Heym, MD (PRINCIPAL_INVESTIGATOR)
Texas Children's Hospital/Baylor College of MedicineHoustonTexas77030
Eric Schafer, MD
Primary Children's HospitalSalt Lake CityUtah84113
Anupam Verma, MD (PRINCIPAL_INVESTIGATOR)
Seattle Children's HospitalSeattleWashington98105
Adam Lamble, MD (PRINCIPAL_INVESTIGATOR)
Children's Hospital of WisconsinMilwaukeeWisconsin53226
Zachary Graff, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in Los Angeles, CA

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
Children's Hospital Los Angeles· Los Angeles, CAChildren's Hospital Orange County· Orange, CAUCSF School of Medicine· San Francisco, CAChildren's Hospital Colorado· Denver, COChildren's National Medical Center· Washington D.C., DCUniversity of Miami· Miami, FL

Related Studies