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

NCT05645718 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0312NCI-2022-10168
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if cyclophosphamide, vincristine, and dexamethasone (called mini hyper-CVD) in combination with intrathecal (delivered into the spine) chemotherapy (methotrexate, hydrocortisone, cytarabine) and compressed rituximab, blinatumomab, and inotuzumab ozogamicin (called cRIB) can help to control the disease.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (2)

Leukemia CNS1 or 2

EXPERIMENTAL

Each study block, or cycle, is 28 days. Between every cycle below, Participants will have a 7-day rest period in which no study drug is given.

Drug: Cyclophosphamide; Drug: Vincristine; Drug: Blinatumomab; Drug: Methotrexate; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Prednisone; Drug: Pegfilgrastim; Drug: Inotuzumab ozogamicin; Drug: Rituximab; Drug: Dexamethasone

Leukemia CNS 3

EXPERIMENTAL

Each study block, or cycle, is 28 days. Between every cycle below, Participants will have a 7-day rest period in which no study drug is given.

Drug: Cyclophosphamide; Drug: Vincristine; Drug: Blinatumomab; Drug: Methotrexate; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Prednisone; Drug: Pegfilgrastim; Drug: Inotuzumab ozogamicin; Drug: Rituximab; Drug: Dexamethasone

Interventions

Cyclophosphamide DRUG

Given by (IV) vein

Also known as: Cytoxan®, Neosar®

Leukemia CNS 3; Leukemia CNS1 or 2

Vincristine DRUG

Given by (IV) vein

Leukemia CNS 3; Leukemia CNS1 or 2

Blinatumomab DRUG

Given by (IV) vein

Leukemia CNS 3; Leukemia CNS1 or 2

Methotrexate DRUG

Given by (IV) vein

Leukemia CNS 3; Leukemia CNS1 or 2

Cytarabine DRUG

Given by (IV) vein

Also known as: Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochloride

Leukemia CNS 3; Leukemia CNS1 or 2

Prednisone DRUG

Given by PO

Leukemia CNS 3; Leukemia CNS1 or 2

Pegfilgrastim DRUG

Given by (IV) vein

Also known as: NeulastaTM, PEG-G-CSF

Leukemia CNS 3; Leukemia CNS1 or 2

Inotuzumab ozogamicin DRUG

Given by (IV) vein

Also known as: CMC-544

Leukemia CNS 3; Leukemia CNS1 or 2

Rituximab DRUG

Given by (IV) vein

Also known as: Rituxan

Leukemia CNS 3; Leukemia CNS1 or 2

Dexamethasone DRUG

Given by (IV) vein

Also known as: Decadron

Leukemia CNS 3; Leukemia CNS1 or 2

Mercaptopurine DRUG

Given by (IV) vein

Also known as: 6-mercaptopurine, Purinethol®, 6-MP

Leukemia CNS 3; Leukemia CNS1 or 2

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia

Interventions

Cyclophosphamide; Vincristine; blinatumomab; Methotrexate; Cytarabine; Mercaptopurine; Prednisone; pegfilgrastim; pegylated granulocyte colony-stimulating factor, human; Inotuzumab Ozogamicin; Rituximab; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Pregnadienetriols; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids

Study Officials

• David McCall, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David McCall, MD

CONTACT

(713) 792-6604; dmccall1@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: December 9, 2022
• Study Start: July 14, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)