Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax

Part of paid clinical trials in New York, New York.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT05192889
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

  • Refractory Acute Lymphoblastic Leukemia
  • Relapsed Acute Lymphoblastic Leukemia

Eligibility Criteria

Sex
ALL
Age
4 Years - 30 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Given oral (PO).
  • Navitoclax — DRUG
    Given oral (PO).
  • Dexamethasone — DRUG
    Given orally (PO) or intravenously (IV).
  • Vincristine — DRUG
    Given intravenously (IV).
  • Calaspargase Pegol — DRUG
    Given intravenously (IV).
  • Dasatinib — DRUG
    Given oral (PO).
  • Cytarabine — DRUG
    Given intravenously (IV) or Intrathecal (IT).
  • Blinatumomab — BIOLOGICAL
    Given intravenously (IV).
  • Methotrexate — DRUG
    Given intravenously (IV), oral (PO), or Intrathecal (IT).
  • Mercaptopurine — DRUG
    Given oral (PO).
  • Cyclophosphamide — DRUG
    Given intravenously (IV).
  • Etoposide — DRUG
    Given intravenously (IV).
  • Leucovorin — DRUG
    Given oral (PO) or intravenously (IV).
  • Intrathecal Triples — DRUG
    Given Intrathecal (IT).
  • Pegaspargase — DRUG
    May be used in place of Calaspargase Pegol where available. Given intravenously (IV) or intramuscularly (IM).
  • Erwinia asparaginase — DRUG
    To be used in case of hypersensitivity or intolerance to Calaspargase Pegol or Pegaspargase. Given intravenously (IV) or intramuscularly (IM).
  • Radiation — RADIATION
    See detailed description section.

Study Details

This is a phase I/II clinical trial evaluating the activity of combination chemotherapy with venetoclax and navitoclax in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) and assessing the combination dose of venetoclax combinations with either blinatumomab for CD19-positive patients or navitoclax and high-dose cytarabine for CD19-negative patients. Primary Objectives * To compare Minimal Residual Disease (MRD)-negative CR/CRi rate in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) following Block 1 therapy with venetoclax and navitoclax based reinduction to historical controls. * To identify the recommended phase 2 combination dose (RP2D) of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. Secondary Objectives * To estimate the tolerability and activity of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. * To describe event-free and overall survival in patients treated with this regimen. Exploratory Objectives * To evaluate MRD-negative CR/CRi rates in each prespecified groups: late first relapse B-ALL; early first relapse and second or greater relapse B-ALL; and relapsed T-ALL. * To identify drug sensitivity patterns in patient samples prior to and after receiving combination therapy and evaluate mechanisms of disease resistance/ escape. * To explore immune subsets during and after this regimen. * Evaluate response to therapy in rare relapse patient subsets. * Explore breakthrough infections in children and young adults with relapsed or refractory ALL

Key Dates

Start date
Aug 25, 2022
Status verified
Sep 2025
Primary completion
Jun 13, 2024
Completion
Feb 28, 2027

Study Design

Enrollment
35 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Block 1
    All eligible patients receive intervention according to the Detailed Description section with the following: Venetoclax, Navitoclax, Dexamethasone, Vincristine, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Dasatinib, Leucovorin, Intrathecal (IT) MHA (methotrexate/hydrocortisone/cytarabine)
  • Experimental: Block 2
    Block 2a Therapy: Patients receive intervention according to the Detailed Description section with the following: Venetoclax, Navitoclax, Dexamethasone, Cytarabine, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Dasatinib, IT MHA, Radiation Block 2b Therapy: Patients receive intervention according to the Detailed Description section with the following: Venetoclax, Blinatumomab, Dexamethasone, Dasatinib, IT MHA Following Block 2 of therapy, late (≥36 months from diagnosis) first relapse B-ALL who are MRD negative after Block 1 will continue chemotherapy using adapted R3 intensification, interim, and continuation therapies. Patients receive intervention according to the Detailed Description section with the following: Methotrexate, Mercaptopurine, IT MHA, Leucovorin, Dexamethasone, Vincristine, Cyclophosphamide, Etoposide, Cytarabine, Dasatinib, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Radiation

Primary Outcome Measure

Number of Participants With Minimal Residual Disease (MRD)-Negative Response [ Time Frame: 4 weeks from start of therapy ]

Locations (2)

FacilityCityStateZIPSite coordinators
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065-
St. Jude Children's Research HospitalMemphisTennessee38105-

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By research site
Memorial Sloan Kettering Cancer Center· New York, NYSt. Jude Children's Research Hospital· Memphis, TN

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