Pediatric-type Therapy With Pre-transplant Blinatumomab for HR Patients - Phase II Study

Sponsor
Israeli Medical Association (Other)
Overall Status
Recruiting
CT.gov ID
NCT04334993
Collaborator
(none)
110
4
1
51.9
27.5
0.5

Study Details

Study Description

Brief Summary

Despite recent therapeutic advancements, the outcome of young adults with Philadelphia-negative (Ph-neg) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) remains unsatisfactory, especially in those patients with high-risk disease features. In young adults pediatric-based chemotherapy approaches improve outcome. Furthermore, there is evidence that pre-transplant antibody-based therapy may render patients with positive minimal residual disease (MRD+) to an MRD-negative status (MRD-) and that this may be associated with improved post-transplant outcome.

This is prospective study to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be performed.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a national, multicenter, phase II clinical trial to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be assessed.

Young-adult patients eligible with Ph-neg ALL, LBL and mixed phenotype acute leukemia (MPAL) will undergo risk stratification and started on the pediatric Italian Association of Pediatric Hematology Oncology-Berlin-Frankfurt-Münster (AIEOP-BFM) 2009 protocol. Patients defined as having non-high-risk disease features (non-HR) as defined by MRD and/or cytogenetic criteria will complete the non-HR chemotherapy arm per protocol. Patients designated as having HR disease features after 2 induction blocks will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation. All patients will be centrally assessed for MRD and for Ph-like status.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
110 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is a national, multicenter, phase II clinical trialThis is a national, multicenter, phase II clinical trial
Masking:
None (Open Label)
Masking Description:
NR
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Single Arm Trial to Assess the Safety and Efficacy of a Pediatric Approach to for Young Adults With Acute Lymphoblastic Leukemia With Blinatumomab Therapy for High-risk Patients Prior to Allogeneic Transplantation
Actual Study Start Date :
Jan 1, 2021
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
May 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Blinatumomab pre-transplant to high risk Ph-negative ALL pts.

Patients designated high risk based on protocol will receive 2 cycles of therapy followed by allogeneic transplantation. Patients ≥45 kg (fixed dose): Cycles 1 and 2: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle.

Drug: Blinatumomab
Patients with high risk disease features after 2 induction blocks as defined per protocol will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation.
Other Names:
  • AIEOP-BFM 2009 protocol - multiagent chemothertapy protocol backbone
  • Outcome Measures

    Primary Outcome Measures

    1. Event-free survival (EFS) [2 years]

      Measured from the date of entry on study until treatment failure, relapse from CR, or death from any cause, whichever occurs first

    Secondary Outcome Measures

    1. Overall survival (OS) [2 years]

      Measured from the date of entry on study until until death from any cause

    2. Early death during induction [60 days]

      Death during the first 60 days from entering study from any cause

    3. MRD status [MRD will be assess by PCR after induction I (day 33), after induction II (week 12), after blinatumomab therapy (prior to HSCT) and at days 30 and 100 post alloHSCT.]

      MRD status pre- and post-antibody-based therapy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Age ≥ 18 years and <30 years of age at the time of signing the informed consent document.

    2. Have a documented diagnosis of Ph-neg ALL, LBL or MPAL according to the WHO 2016 classification (appendix I).

    3. Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:

    Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following EOT; and have a negative serum or urine pregnancy test (investigator's discretion; sensitivity at least 25 mIU/mL) at screening; and have a negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study therapy in the treatment phase (note that the screening serum pregnancy test can be used as the test prior to starting study therapy in treatment phase if it is performed within the 72-hour timeframe).

    1. Male subjects with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose of study drug.

    2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

    3. Able to adhere to the study visit schedule and other protocol requirements.

    Exclusion Criteria:
    1. Age <18 or over 30 years at the time of signing the informed consent document.

    2. Ph-positive disease.

    3. Known Human Immunodeficiency Virus (HIV).

    4. Known or suspected hypersensitivity to any of the study drugs.

    5. Pregnant or lactating females.

    6. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

    7. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

    8. Participation to an investigational drug trial in the last month before randomization.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rambam Medical Center Haifa Israel
    2 Shaarei Tzedek Medical Center Jerusalem Israel
    3 Rabin Medical Center Petah Tikva Israel 49100
    4 Tel Aviv Medical Center Tel Aviv Israel

    Sponsors and Collaborators

    • Israeli Medical Association

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Israeli Medical Association
    ClinicalTrials.gov Identifier:
    NCT04334993
    Other Study ID Numbers:
    • AYA001
    First Posted:
    Apr 6, 2020
    Last Update Posted:
    May 7, 2021
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Israeli Medical Association
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 7, 2021