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Trials / Recruiting

RecruitingNCT07133997

Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia

A Phase 1/1b Study Evaluating Asparaginase Erwinia Chrysanthemi- Recombinant-Rywn (Recombinant Erwinia Asparaginase) and Venetoclax in Combination With Blinatumomab in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
26 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
12 Years – 55 Years
Healthy volunteers
Not accepted

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 well the combination works in treating patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Asparaginase Erwinia chrysanthemi, a type of protein synthesis inhibitor, is a drug that is made up of the enzyme asparaginase, which comes from the bacterium Erwinia chrysanthemi. It is used in people who cannot take asparaginase that comes from the bacterium E. coli. Asparaginase Erwinia chrysanthemi breaks down the amino acid asparagine and may stop the growth of cancer cells that need asparagine to grow. It may also kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a drug used to treat certain types of B-cell acute lymphoblastic leukemia that are CD19 positive (expresses the protein CD19). Blinatumomab binds to CD19, which is found on most B cells (a type of white blood cell) and some types of leukemia cells. It also binds to a protein called CD3, which is found on T cells (another type of white blood cell). This may help the immune system kill cancer cells. Blinatumomab is a type of bispecific T-cell engager. Giving asparaginase Erwinia chrysanthemi and venetoclax in combination with blinatumomab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory ALL.

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 for the target population by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase I) II. Determine the recommended phase 2 schedule (RP2S) of recombinant Erwinia asparaginase and venetoclax in combination with blinatumomab. (Phase I) III. Estimate the anti-tumor efficacy of recombinant Erwinia asparaginase and venetoclax in combination with blinatumomab as assessed by composite remission (including complete remission (CR), CR with partial hematologic recovery (CRh) and CR with incomplete hematologic recover (CRi) rate. (Expansion Phase) SECONDARY OBJECTIVES: I. Evaluate the safety of recombinant Erwinia asparaginase in combination with blinatumomab and venetoclax at expansion phase. II. Estimate minimal residual disease (MRD) negativity (-) rate at the end of each cycle (by flow MRD and Clonoseq). III. Among transplant eligible patients, determine the number and proportion of patients who bridge directly from trial therapy to allogeneic hematopoietic stem cell transplant (alloHSCT). EXPLORATORY OBJECTIVES: I. Explore BH3 profiling on pretreatment bone marrow aspirate to predict response to blinatumomab with recombinant Erwinia asparaginase and venetoclax. II. Explore role of somatic mutations in pretreatment bone marrow biopsy to predict response to blinatumomab with recombinant Erwinia asparaginase and venetoclax. III. Examine changes in cell composition-both leukemic and non-leukemic-before and after treatment. IV. Estimate the proportion of patients maintaining adequate nadir serum asparaginase activity (≥ 0.1 IU/mL) at 48 hours post last dose of recombinant Erwinia asparaginase. V. Immune profiling of ALL blasts. OUTLINE: PRE-PHASE TREATMENT/BRIDGE THERAPY: Starting days -7 to -5, patients may optionally receive cyclophosphamide and vincristine on day 1 and prednisone on days 1-5. TREATMENT: Patients receive asparaginase Erwinia chrysanthemi intramuscularly (IM) on days 1,3, 5, 7, 9, 11, and 13, venetoclax orally (PO) once daily (QD) on days 1-14 or once every other day (QOD) on days 1, 3, 5, 7, 9, 11, and 13 of each cycle and blinatumomab continuous intravenously (CIV) on days 8-35 of cycle 1 and on days 1-28 of cycle 2. Cycles repeat every 49 days for cycle 1 and 42 days for cycle 2 for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) and multigated acquisition scan (MUGA) at screening and bone marrow aspiration and biopsy, blood sample collection, and lumbar puncture throughout the study. After completion of study treatment, patients are followed up at 30 days.

Conditions

Interventions

TypeNameDescription
DRUGAsparaginase Erwinia chrysanthemiGiven IM
PROCEDUREBiospecimen CollectionUndergo blood sample collection
BIOLOGICALBlinatumomabGiven CIV
PROCEDUREBone Marrow AspirationUndergo bone marrow aspiration and biopsy
PROCEDUREBone Marrow BiopsyUndergo bone marrow aspiration and biopsy
DRUGCyclophosphamideGiven cyclophosphamide
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDURELumbar PunctureUndergo lumbar puncture
PROCEDUREMultigated Acquisition ScanUndergo MUGA
DRUGVenetoclaxGiven PO
DRUGVincristineGiven vincristine

Timeline

Start date
2026-06-01
Primary completion
2028-06-01
Completion
2028-06-01
First posted
2025-08-21
Last updated
2026-04-07

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT07133997. Inclusion in this directory is not an endorsement.