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

NCT ID: NCT05645718

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-14
• Study Completion Date: 2029-12-31

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.

Detailed Description

Primary Objective:

--To evaluate the clinical efficacy of the sequential combination of mini-hyper-CVD with inotuzumab ozogamicin and blinatumomab and rituximab in relapsed B-cell acute lymphoblastic leukemia (ALL) patients, based upon the complete response rate (CR).

Secondary Objectives:

• To summarize efficacy per response rate, overall survival (OS), event free survival (EFS), and minimal residual disease (MRD) negativity rate.
• To evaluate the safety of this combination.

Exploratory Objectives:

--To summarize associations between genomic alterations in ALL (current biomarker expression of the disease) with relation to the incidence of transition to HSCT in patients with PR or stable disease (SD) after the induction cycle(s).

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Leukemia CNS1 or 2

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.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given by (IV) vein

Vincristine

Intervention Type: DRUG

Given by (IV) vein

Blinatumomab

Intervention Type: DRUG

Given by (IV) vein

Methotrexate

Intervention Type: DRUG

Given by (IV) vein

Cytarabine

Intervention Type: DRUG

Given by (IV) vein

Mercaptopurine

Intervention Type: DRUG

Given by (IV) vein

Prednisone

Intervention Type: DRUG

Given by PO

Pegfilgrastim

Intervention Type: DRUG

Given by (IV) vein

Inotuzumab ozogamicin

Intervention Type: DRUG

Given by (IV) vein

Rituximab

Intervention Type: DRUG

Given by (IV) vein

Dexamethasone

Intervention Type: DRUG

Given by (IV) vein

Leukemia CNS 3

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.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given by (IV) vein

Vincristine

Intervention Type: DRUG

Given by (IV) vein

Blinatumomab

Intervention Type: DRUG

Given by (IV) vein

Methotrexate

Intervention Type: DRUG

Given by (IV) vein

Cytarabine

Intervention Type: DRUG

Given by (IV) vein

Mercaptopurine

Intervention Type: DRUG

Given by (IV) vein

Prednisone

Intervention Type: DRUG

Given by PO

Pegfilgrastim

Intervention Type: DRUG

Given by (IV) vein

Inotuzumab ozogamicin

Intervention Type: DRUG

Given by (IV) vein

Rituximab

Intervention Type: DRUG

Given by (IV) vein

Dexamethasone

Intervention Type: DRUG

Given by (IV) vein

Interventions

Cyclophosphamide

Given by (IV) vein

Intervention Type: DRUG

Vincristine

Given by (IV) vein

Intervention Type: DRUG

Blinatumomab

Given by (IV) vein

Intervention Type: DRUG

Methotrexate

Given by (IV) vein

Intervention Type: DRUG

Cytarabine

Given by (IV) vein

Intervention Type: DRUG

Mercaptopurine

Given by (IV) vein

Intervention Type: DRUG

Prednisone

Given by PO

Intervention Type: DRUG

Pegfilgrastim

Given by (IV) vein

Intervention Type: DRUG

Inotuzumab ozogamicin

Given by (IV) vein

Intervention Type: DRUG

Rituximab

Given by (IV) vein

Intervention Type: DRUG

Dexamethasone

Given by (IV) vein

Intervention Type: DRUG

Other Intervention Names

Cytoxan®; Neosar®; Ara-C; Cytosar®; DepoCyt™; Cytosine arabinosine hydrochloride; 6-mercaptopurine; Purinethol®; 6-MP; NeulastaTM; PEG-G-CSF; CMC-544; Rituxan; Decadron

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.

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David McCall, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

David McCall, MD

Role: CONTACT

dmccall1@mdanderson.org

(713) 792-6604

Facility Contacts

David Mc Call, MD

Role: primary

dmccall1@mdanderson.org

713-792-6604

Related Links

http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

NCI-2022-10168

Identifier Type: OTHER

Identifier Source: secondary_id

2022-0312

Identifier Type: -

Identifier Source: org_study_id