ABL001 + Dasatinib + Prednisone + Blinatumomab in BCR-ABL+ B-ALL or CML

NCT03595917 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-170
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is evaluating a drug called ABL001 taken in combination with dasatinib (Sprycel®) and prednisone (a steroid) as a possible treatment for B-cell Acute Lymphoblastic Leukemia that is BCR-ABL positive (BCR-ABL+ B-ALL) or Chronic Myeloid Leukemia (CML) in lymphoid blast crisis. BCR-ABL+ B-ALL is also called Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL). It is expected that 40-65 people will take part in this research study.

• ABL001
• Dasatinib (Sprycel®)
• Prednisone
• Blinatumomab

Conditions

B-cell Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia (CML) in Lymphoid Blast Crisis; Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Ph+ ALL

Keywords

B-cell Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia (CML) in lymphoid blast crisis; Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL).

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of ABL001

  To define the maximum tolerated dose (MTD) of ABL001 for participants with BCR-ABL positive (BCR-ABL+) B-cell acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) in lymphoid blast crisis.

  42 Days

Secondary Outcomes (12)

• Percentage for Participants Achieving Hematologic Remission

  28 Days

• Percentage for Participants Achieving Hematologic Remission

  56 Days

• Percentage for Participants Achieving Hematologic Remission

  85 Days

• Percentage of participants achieving cytogenetic response

  28 Days

• Percentage of participants achieving cytogenetic response

  56 Days

Study Arms (1)

ABL001, Dasatinib, Prednisone, Blinatumomab

EXPERIMENTAL

\- Dose escalation will occur conventional Fibonocci 3+3 dose escalation scheme to determine a recommended phase 2 dose (RP2D) * Dasatinib-Fixed doses oral once a day per cycle * ABL001 is administered orally daily per cycle * Prednisone-Fixed doses oral once a day per cycle. \--- Prednisone will be tapered and stop during cycle 2. * Blinatumomab - intravenous continuous infusion beginning no earlier than cycle 2 day 1 * Blinatumomab - Day 1-28 of each 42-day cycle, cycles 2-6, total of 5 cycles

Drug: ABL001; Drug: Dasatinib; Drug: Prednisone; Drug: Blinatumomab

Interventions

ABL001 DRUG

•ABL001 is administered daily per 28 day cycle

ABL001, Dasatinib, Prednisone, Blinatumomab

Dasatinib DRUG

Fixed doses oral once a day per 28 day cycle

Also known as: Sprycel

ABL001, Dasatinib, Prednisone, Blinatumomab

Prednisone DRUG

Fixed doses oral once a day per 28 day cycle Prednisone will be tapered and stop during cycle 2.

ABL001, Dasatinib, Prednisone, Blinatumomab

Blinatumomab DRUG

By intravenous continuous infusion beginning no earlier than cycle 2 day 1 of protocol therapy Day 1-28 of each 42-day cycle, cycles 2-6, total of 5 cycles

ABL001, Dasatinib, Prednisone, Blinatumomab

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have cytopathologically confirmed CD19+ BCR-ABL1+ acute leukemia (B-cell ALL, mixed phenotype acute leukemia, or CML in lymphoid blast crisis with ≥ 5% lymphoblasts.)22
• BCR-ABL1 positive status may be confirmed by FISH, karyotype analysis, or molecular testing for p210 (b2a2 or b3a2) or p190 (e1a2) transcripts.
• Patients with asymptomatic central nervous system (CNS) disease are eligible and may be treated concurrently with intrathecal chemotherapy.
• Dose escalation: Participants must NOT be suitable for or willing to receive standard intensive induction chemotherapy.
• Dose expansion: Participants aged 18 years and older will be eligible regardless of suitability for intensive induction chemotherapy.
• The following groups are not considered suitable for standard intensive induction chemotherapy:
• Participants who have not received standard intensive induction chemotherapy and are aged ≥ 50 years.
• Participants who have not received standard intensive induction chemotherapy and are aged 18 to 49 years and unfit due to co-morbidity or other factors to receive intensive chemotherapy. Specific criteria that would suggest that a patient is unsuitable for intensive induction chemotherapy include:
• Severe cardiac comorbidity (congestive heart failure or documented cardiomyopathy with EF ≤50%).
• Severe pulmonary comorbidity (documented pulmonary disease with DLCO ≤ 65% or FEV1 ≤ 65%, or dyspnea at rest, or requiring oxygen).
• ECOG performance status of 2 due to medical conditions unrelated to leukemia.
• Any other comorbidity that the physician judges to be incompatible with intensive cytotoxic chemotherapy.
• Participants aged ≥ 18 years with disease that is relapsed or refractory to 1 or more cycles of standard intensive induction chemotherapy.
• ECOG performance status 0-3 (Appendix A). ECOG value of 3 is allowed after documented discussion with PI, if poor performance status is attributed to underlying disease.

You may not qualify if:

• For dose escalation only: Participants suitable for and willing to receive standard intensive induction chemotherapy.
• Patients with a known ABL T315I mutation are excluded. ABL kinase mutation analysis is not recommended for newly diagnosed patient. ABL kinase mutation analysis is recommended for patients with relapsed disease or CML progressed to blast phase on prior TKI, and results should be reviewed prior to enrollment.
• Prior treatment of ALL or CML with dasatinib or ASCIMINIB. Prior receipt of other TKIs and chemotherapy for the treatment of ALL or CML is permitted.
• Any TKI therapy must be discontinued for 5 half-lives prior to initiation of protocol therapy.
• Patient may not have received other chemotherapy, including antibody-based therapy, within 2 weeks of the initiation of protocol therapy with the exception of steroids, hydroxyurea, ATRA, and/or intrathecal chemotherapy.
• Participants who are receiving any other investigational agents for conditions other than ALL must have discontinued those agents 2 weeks prior to the start of study treatment.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome). Patients who have had a gastrectomy are not excluded.
• History of prior or concurrent malignancy requiring current treatment and/or whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Indolent or low risk cancers (i.e. early stage prostate cancer, early stage breast cancer, asymptomatic meningioma) judged to not require treatment and/or have low potential for progression/recurrence after appropriate therapy may be permitted after discussion with overall PI.
• Acute or chronic liver disease (including known active hepatitis B and C infections).
• Screening for hepatitis is not required. Patients with known treated or past exposure viral hepatitis may participate after confirmation of absence of active infection (i.e. negative viral load).
• History of pulmonary arterial hypertension.
• Significant pleural effusions leading to respiratory compromise and need for intervention (i.e. thoracentesis).
• Alcohol abuse requiring medical treatment.
• Participants with a history of or current acute pancreatitis, chronic pancreatitis, or any ongoing pancreatic disease.
• Known human immunodeficiency virus (HIV). Screening is not required.

Sponsors & Collaborators

• Marlise Luskin, MD: lead
• Novartis: collaborator

Study Sites (4)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; Dasatinib; Prednisone; blinatumomab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marlise R. Luskin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marlise R. Luskin, MD

CONTACT

617-632-1906; Marlise_Luskin@DFCI.HARVARD.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 23, 2018
• Study Start: July 24, 2018
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)