Status:
NOT_YET_RECRUITING
Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia
Lead Sponsor:
City of Hope Medical Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Recurrent B Acute Lymphoblastic Leukemia
Refractory B Acute Lymphoblastic Leukemia
Eligibility:
All Genders
12-55 years
Phase:
PHASE1
Brief Summary
This phase I/Ib trial tests the safety and side effects of asparaginase Erwinia chrysanthemi-recombinant-rywn (recombinant Erwinia asparaginase) and venetoclax in combination with blinatumomab and how...
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of asparaginase Erwinia chrysanthemi- recombinant-rywn (recombinant Erwinia asparaginase) and venetoclax in combination with blinatumomab f...
Eligibility Criteria
Inclusion
- Documented informed consent of the participant and/or legally authorized representative
- Age between 12 and 55
- Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS) ≥ 70
- Patients with relapsed or refractory (R/R) CD19 positive (+) B-cell acute lymphoblastic leukemia (B-ALL) according to World Health Organization (WHO) criteria
- Greater than or equal to 5% blasts in the bone marrow
- White blood cell count less than 25 x 10\^9/L prior to initiation of venetoclax. (within 14 days prior to day 1 of protocol therapy) Cytoreduction with hydroxyurea, steroid or a single dose of cyclophosphamide chemotherapy prior to treatment may be required
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to day 1 of protocol therapy) (unless has Gilbert's disease or underlying leukemia, ≤ 3 x ULN)
- Prothrombin time (PT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
- Partial thromboplastin time (PTT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 14 days prior to day 1 of protocol therapy) (Unless it is related to underlying leukemia, then AST ≤ 5 x ULN)
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 14 days prior to day 1 of protocol therapy) (Unless it is related to underlying leukemia, then ALT ≤ 5 x ULN)
- Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 14 days prior to day 1 of protocol therapy)
- Left ventricular ejection fraction (LVEF) ≥ 50% (within 14 days prior to day 1 of protocol therapy)
- Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy
- Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).
Exclusion
- Allogeneic hematopoietic cell transplantation (HCT) within 8 weeks prior to the start of protocol-specific therapy. Subjects must be off all immunosuppression for ≥ 2 weeks
- Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy with the exception of: intrathecal chemotherapy and/or low-dose maintenance therapy (e.g. vina alkaloids, mercaptopurine, methotrexate, or hydroxyurea etc)
- Strong and moderate CYP3A4 inducers and strong CYP3A inhibitors within 7 days prior to day 1 of protocol therapy
- Foods/supplements that are strong inhibitors or strong or moderate inducers of CYP3A (such as grapefruit, Seville oranges, starfruit and St. John's wort) within 3 days prior to initiation of and during study treatment
- Immunotherapy (e.g. rituximab) within 4 weeks before the start of protocol-specified therapy. Prior failed CD19-directed therapy such as prior blinatumomab or CD19-directed chimeric antigen receptor (CAR)-T cells will be allowed if treatment ended \> 4 weeks prior to start of protocol-specific therapy and there is demonstrated continued CD19+ expression
- Must not have received or planning to receive live vaccine while being on study or 2 weeks before and after completion of treatment
- Patients with any prior intolerance leading to discontinuation of pegylated (PEG)-asparaginase due to grade 3 or more pancreatitis or central nervous system thrombosis requiring anticoagulant treatment attributed to the PEG-asparaginase
- Active ALL in the central nervous system (CNS): Presence of \> 5 white blood cells (WBC) per cubic millimeter in the cerebrospinal fluid (CSF) with lymphoblasts present (confirmed by CSF analysis) and/or clinical signs of CNS leukemia. If CSF leukemia is present, subjects will need to receive intrathecal chemotherapy and have documented negative CSF prior to enrollment
- Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication
- History of intracranial thrombosis or history of recurrent thrombosis or grade 3 and greater pulmonary embolism (except for catheter-related thrombosis)
- Participants with history of grade ≥ 3 pancreatitis
- History of alcohol overuse if deemed relevant in investigator's opinion
- Known hypersensitivity to blinatumomab/ recombinant Erwinia asparaginase or to any component of the product formulation, otherwise prior treatment with single agent blinatumomab is allowed
- Uncontrolled active infection
- Clinically significant uncontrolled illness or cirrhosis
- Other active malignancy (except superficial skin cancers squamous cell carcinoma \[SCC\]/basal cell carcinoma \[BCC\], early-stage malignancies ductal carcinoma in-situ \[DCIS\] status post \[s/p\] excision or elevated prostate specific antigen \[PSA\])
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Key Trial Info
Start Date :
January 26 2026
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
May 8 2027
Estimated Enrollment :
26 Patients enrolled
Trial Details
Trial ID
NCT07133997
Start Date
January 26 2026
End Date
May 8 2027
Last Update
December 15 2025
Active Locations (1)
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1
City of Hope Medical Center
Duarte, California, United States, 91010