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

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

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.

Study Overview

• Status: Recruiting
• Conditions: High-Risk Cancer; Philadelphia-Negative ALL
• Intervention / Treatment: Drug: Blinatumomab

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 Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ofir Wolach, MD; Phone Number: +972-3-9378116; Email: ofirw@clalit.org.il

Study Locations

• Israel
  • Haifa, Israel
    • Recruiting
    • Rambam Medical Center
    • Contact: Yishai Ofran, MD; Email: y_ofran@rambam.health.gov.il
  • Jerusalem, Israel
    • Recruiting
    • Shaarei Tzedek Medical Center
    • Contact: Jacob Rowe, MD; Email: rowe@rambam.health.gov.il
  • Petah Tikva, Israel, 49100
    • Recruiting
    • Rabin Medical Center
    • Contact: Ofir Wolach, MD; Phone Number: +972-3-937-8116; Email: ofirw@clalit.org.il
    • Contact: Miri Pinhasov, MA; Phone Number: +972-3-9378078; Email: miripi@clalit.org.il
  • Tel Aviv, Israel
    • Not yet recruiting
    • Tel Aviv Medical Center
    • Contact: Yakir Moshe, MD PhD; Email: yakirm@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

4. 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.
5. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Measured from the date of entry on study until treatment failure, relapse from CR, or death from any cause, whichever occurs first	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Measured from the date of entry on study until until death from any cause	2 years
Early death during induction	Death during the first 60 days from entering study from any cause	60 days
MRD status	MRD status pre- and post-antibody-based therapy	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.

Collaborators and Investigators

• Sponsor: Israeli Medical Association

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Blinatumomab; Allogeneic transplantation; Philadelphia-Negative ALL; Pediatric therapy
• Additional Relevant MeSH Terms: Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: AYA001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: All data will be coded and uploaded to an electronic CRF (red-cap) to manage abnd analyze data

Drug and device information, study documents

• 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