New treatment approach for pediatric patients with relapsed B-cell leukemia

Phase II Study of Pedi-cRIB: Mini-Hyper-CVD With Condensed Rituximab, Inotuzumab Ozogamicin and Blinatumomab (cRIB) for Relapsed Therapy for Pediatric With B-Cell Lineage Acute Lymphocytic Leukemia

This study is testing a new combination treatment for kids with relapsed B-cell leukemia to see if it helps them get better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 1 Year to 25 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: rituximab, inotuzumab, chemotherapy, radiation, doxorubicin, blinatumomab, methotrexate, cyclophosphamide
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05645718 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a combination therapy called mini-hyper-CVD, which includes cyclophosphamide, vincristine, and dexamethasone, along with intrathecal chemotherapy and a regimen of rituximab, blinatumomab, and inotuzumab ozogamicin for pediatric patients with relapsed B-cell acute lymphoblastic leukemia (ALL). The primary goal is to assess the complete response rate to this treatment, while secondary objectives include overall survival, event-free survival, and safety evaluations. Additionally, the study aims to explore the relationship between genomic alterations in ALL and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are pediatric, adolescent, or young adult patients aged 1 to 25 years with relapsed or primary refractory B-cell acute lymphoblastic leukemia.

Not a fit: Patients who are not experiencing relapse or are not within the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve disease control and survival rates in pediatric patients with relapsed B-cell leukemia.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating relapsed B-cell leukemia, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Pediatric, adolescent, or young adult patients with B-ALL as per NCCN v2.2021 and WHO classification in relapse or primary refractory and, either/both of the following: • Unable to receive anthracyclines (see section 3.1.8) or is PEG-asparaginase intolerant.

  * For leukemia: Patients must have ≥ 5% blasts expressing CD19 and CD22 in the bone marrow as assessed by morphology or flow cytometry. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood.
  * If patient does not have CD20, they can still be enrolled but will not receive rituximab.
* Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are \> 16 years old.
* Patients with asymptomatic CNS leukemia are eligible (see also Exclusion Criterion 3.2.2.)
* Age \> = 1 years of age and less than 25 years of age.
* The following baseline laboratory data:

  * Total serum bilirubin ≤1.5x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN.
  * Adequate renal function per age51 unless related to the disease. Estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric patients or Cockcroft Gault formula for adults).
  * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x ULN; ≤5 x ULN in case of suspected leukemic liver involvement
* Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and 30 days after the last treatment and 8 months after the last dose of inotuzumab and 12 months after the last dose of rituximab. Effective methods of birth control include:

  * Birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin)
  * Intrauterine devices (IUDs)
  * Condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide
  * Abstinence
* Males need to inform the doctor right away if the partner becomes pregnant or suspects pregnancy. While in this study and for 30 days after the last treatment the patient should not donate sperm for the purposes of reproduction. He will need to use a condom while in this study and for 30 days after the last treatment and 5 months after the last dose of inotuzumab.
* Patients with cardiac disease, include but not limited to: (Left ventricular ejection fraction (EF) \< 50% (as determined by the Biplane Simpson method) (but not per exclusion criteria 3.2.3.1), or who have received \>450mg/m2 of doxorubicin and cannot receive anthracyclines.

Exclusion Criteria:

* Past or current history of a secondary or other primary tumor or a chronic myeloid leukemia (CML) blast crisis with exception of:

  * Curatively treated non-melanomatous skin cancer
  * Other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 2 years
* Presence of clinically significant uncontrolled CNS pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis. Presence of the following are allowed: headaches, vomiting, nerve palsy
* Medical history of cardiovascular disease such as:

  ° Clinically significant cardiac disease including congestive heart failure (NYHA class III or IV) or arrhythmia or conduction abnormality requiring medication
* Patients with uncontrolled, active infections (viral, bacterial, or fungal). Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
* Known active hepatitis B or C infection or known seropositivity for HIV.
* Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse.
* Active acute/chronic Graft-versus-Host Disease (GvHD) requiring systemic treatment; or receiving immunosuppression for GvHD prophylaxis within 2 weeks from the start of study therapy.
* If patient has not recovered (as deemed by the investigator) from previous chemotherapy, surgery, radiation before the start of study drugs.

  ° To reduce the circulating blast count or palliation, the following are allowed prior to starting: Single dose intravenous cytarabine, steroids or hydroxyurea. No washout necessary for these agents.
* Females who are pregnant or lactating.
* Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards.
* Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated Protocol 2022-0312 V3 Dated 11/9/2023 Property of Leukemia at MD Anderson 17 with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.
* Patients with Trisomy 21, or bone marrow failure syndromes are not eligible.
* Prior history of allergic reaction to any of the agents.
* Patients who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.
* Patients may be excluded if they are currently enrolled in another ongoing clinical trial with investigational products

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: David McCall, MD — M.D. Anderson Cancer Center
• Study coordinator: David McCall, MD

Conditions Leukemia