Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

NCT04329325 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 19-343
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test whether blinatumomab in combination with TKI therapy (such as dasatinib) is an effective treatment for people with Ph+ ALL. Researchers want to improve the response to standard-of-care treatment of corticosteroids + TKI therapy by adding the study drug, blinatumomab.

Conditions

Acute Lymphoblastic Leukemia; Philadelphia Chromosome-Positive

Keywords

Blinatumomab; Concurrent Oral Tyrosine Kinase Inhibitor; Chemotherapy-Sparing Induction; 19-343

Outcome Measures

Primary Outcomes (1)

• Proportion of evaluable patients achieving complete molecular response

  (MRD negativity by flow cytometry and quantitative PCR of BCR-ABL transcripts) at any time during TKI + corticosteroid induction or consolidation with up to 3 cycles of blinatumomab in combination with TKI.

  7 months

Secondary Outcomes (7)

• Frequency, severity, and co-occurrence of treatment-related grade 3-4 toxicities

  13 months

• Proportion of evaluable patients with CMR or molecular MRD positivity with MRD negativity by flow cytometry at any time during induction or consolidation.

  7 months

• Duration of CMR among patients achieving MRD negativity after TKI + corticosteroid induction, followed by 1-3 cycles of blinatumomab in combination with an oral TKI.

  2 years

• Cumulative incidence of morphologic and molecular relapse following consolidative therapy with blinatumomab in combination with an oral TKI

  2 years

• Event-free survival following consolidative therapy with blinatumomab in combination with an oral TKI.

  2 years

Other Outcomes (2)

• Frequency, type, and co-occurrence of ABL kinase mutations

  2 years

• Frequency, type, and co-occurrence of new somatic mutations

  2 years

Study Arms (1)

Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI)

EXPERIMENTAL

Patients may receive steroids and hydroxyurea pre-study entry and receive a 7-day steroid prephase before starting TKI therapy. Planned initial TKI is dasatinib 140 mg daily; dasatinib dose may be reduced or TKI may be changed to a different agent under certain conditions. Induction consists of continuous TKI + 24 days of dexamethasone, followed by taper of dexamethasone, with bone marrow aspirate/biopsy (BMA) and CNS prophylaxis at days 22 and 43. Patients achieving morphologic complete response post-induction proceed to consolidation with up to 3 cycles of blinatumomab (28-day cycles, 14 days between cycles) + TKI, with BMA and CNS prophylaxis between cycles. Patients achieving complete molecular response may proceed to maintenance with up to 4 more cycles of blinatumomab (28-day cycles with 28 days between cycles) + TKI, with CNS prophylaxis between cycles and BMA after cycles 5 and 7. Patients can come off study to undergo allogeneic hematopoietic cell transplantation at any time.

Biological: Blinatumomab; Drug: dasatinib; Drug: dexamethasone; Drug: methotrexate

Interventions

Blinatumomab BIOLOGICAL

Please see detailed summary.

Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI)

dasatinib DRUG

Please see detailed summary.

Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI)

dexamethasone DRUG

Please see detailed summary.

Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI)

methotrexate DRUG

Please see detailed summary.

Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give informed consent
• Age ≥ 18 years of age
• Direct bilirubin ≤2x upper limit of normal (ULN), AST and ALT ≤10x upper limit of normal (ULN). Higher bilirubin and AST/ALT levels are acceptable if thought related to Ph+ ALL.
• Histology confirmed by enrolling institution Confirmed diagnosis of acute lymphoblastic leukemia (ALL) by morphology, immunohistochemistry, and/or multiparameter flow cytometry, with confirmation of Philadelphia chromosome positivity (Ph+) by cytogenetic studies (karyotype/FISH), molecular studies (BCRABL1 fusion transcripts), or targeted RNA sequencing

You may not qualify if:

• Amenable to practicing an effective method of birth control during treatment and for at least 3 months following treatment on study
• ECOG performance status 0-2
• Philadelphia chromosome-negative ALL
• Mature B-cell ALL (e.g. Burkitt leukemia/lymphoma)
• Active extramedullary disease at time of study entry, including known CNS-3 disease (≥5 WBC/microliter and positive cytology or flow cytometry). Note: LP and/or CNS imaging prior to treatment initiation is not required, but if the patient is found to have active CNS-3 disease (by LP) or evidence of CNS involvement on imaging in the course of evaluation of clinical findings, enrollment is not permissible.
• Presence of known ABL kinase mutations conferring resistance to dasatinib at time of study entry, including T315I mutation. Note: ABL mutation testing prior to treatment initiation is neither recommended nor required, but if results of such mutation testing are known, enrollment of a patient with known ABL kinase mutations conferring dasatinib resistance is not permissible.
• Unable to tolerate oral medication.
• Creatinine \>1.5x upper limit of normal and estimated GFR \<30 mL/min (based on 24-hour urine collection to determine creatine clearance or CKD-EPI equation) NOTE: Meeting EITHER the blood creatinine level standard OR the estimated GFR standard (based on 24 hour urine collection OR CKD-EPI equation) is required for eligibility. Subjects are excluded only if BOTH criteria are not met.
• Heart disease meeting one or more of the following criteria:
• New York Heart Association (NYHA) stage III or IV congestive heart failure
• Myocardial infarction \<6 months prior to enrollment
• History of clinically significant ventricular arrhythmia
• History of cardiomyopathy with left ventricular ejection fraction ≤20%
• Pre-treatment Fredericia-adjusted QTc (QTcF) of \>500 msec, unless the patient is thought to be an acceptable candidate for dasatinib after consultation with a cardiologist (including, but not limited to situations in which QTcF is thought not representative of true length of repolarization due to pre-existing bundle branch block or ventricular pacing)
• Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen) are ineligible

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Amgen: collaborator

Study Sites (2)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

blinatumomab; Dasatinib; Dexamethasone; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mark Geyer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is an open-label single arm phase II study with a Simon's minimax two-stage for the treatment of adults with newly diagnosed Ph+ ALL.

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: March 30, 2020
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2)