Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax

Summary

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

Conditions

• Refractory Acute Lymphoblastic Leukemia
• Relapsed Acute Lymphoblastic Leukemia

Interventions

DRUG

Venetoclax

Given oral (PO).

DRUG

Navitoclax

Given oral (PO).

DRUG

Dexamethasone

Given orally (PO) or intravenously (IV).

DRUG

Vincristine

Given intravenously (IV).

DRUG

Calaspargase Pegol

Given intravenously (IV).

DRUG

Dasatinib

Given oral (PO).

DRUG

Cytarabine

Given intravenously (IV) or Intrathecal (IT).

BIOLOGICAL

Blinatumomab

Given intravenously (IV).

DRUG

Methotrexate

Given intravenously (IV), oral (PO), or Intrathecal (IT).

DRUG

Mercaptopurine

Given oral (PO).

DRUG

Cyclophosphamide

Given intravenously (IV).

DRUG

Etoposide

Given intravenously (IV).

DRUG

Leucovorin

Given oral (PO) or intravenously (IV).

DRUG

Intrathecal Triples

Given Intrathecal (IT).

DRUG

Pegaspargase

May be used in place of Calaspargase Pegol where available. Given intravenously (IV) or intramuscularly (IM).

DRUG

Erwinia asparaginase

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.

Sponsors & Collaborators

• AbbVie

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Seth E. Karol, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

4 Years

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-25

Primary Completion

2024-06-13

Completion

2027-02-28

FDA Drug

Yes

Countries

• United States

Study Locations