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

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05645718
Collaborator
(none)
27
1
2
80.1
0.3

Study Details

Study Description

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
27 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Anticipated Study Start Date :
Apr 30, 2023
Anticipated Primary Completion Date :
Dec 31, 2027
Anticipated Study Completion Date :
Dec 31, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Cyclophosphamide
Given by (IV) vein
Other Names:
  • Cytoxan®
  • Neosar®
  • Drug: Vincristine
    Given by (IV) vein

    Drug: Blinatumomab
    Given by (IV) vein

    Drug: Methotrexate
    Given by (IV) vein

    Drug: Cytarabine
    Given by (IV) vein
    Other Names:
  • Ara-C
  • Cytosar®
  • DepoCyt™
  • Cytosine arabinosine hydrochloride
  • Drug: Mercaptopurine
    Given by (IV) vein
    Other Names:
  • 6-mercaptopurine
  • Purinethol®
  • 6-MP
  • Drug: Prednisone
    Given by PO

    Drug: Pegfilgrastim
    Given by (IV) vein
    Other Names:
  • NeulastaTM
  • PEG-G-CSF
  • Drug: Inotuzumab ozogamicin
    Given by (IV) vein
    Other Names:
  • CMC-544
  • Drug: Rituximab
    Given by (IV) vein
    Other Names:
  • Rituxan
  • Drug: Dexamethasone
    Given by (IV) vein
    Other Names:
  • Decadron
  • Experimental: 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.

    Drug: Cyclophosphamide
    Given by (IV) vein
    Other Names:
  • Cytoxan®
  • Neosar®
  • Drug: Vincristine
    Given by (IV) vein

    Drug: Blinatumomab
    Given by (IV) vein

    Drug: Methotrexate
    Given by (IV) vein

    Drug: Cytarabine
    Given by (IV) vein
    Other Names:
  • Ara-C
  • Cytosar®
  • DepoCyt™
  • Cytosine arabinosine hydrochloride
  • Drug: Mercaptopurine
    Given by (IV) vein
    Other Names:
  • 6-mercaptopurine
  • Purinethol®
  • 6-MP
  • Drug: Prednisone
    Given by PO

    Drug: Pegfilgrastim
    Given by (IV) vein
    Other Names:
  • NeulastaTM
  • PEG-G-CSF
  • Drug: Inotuzumab ozogamicin
    Given by (IV) vein
    Other Names:
  • CMC-544
  • Drug: Rituximab
    Given by (IV) vein
    Other Names:
  • Rituxan
  • Drug: Dexamethasone
    Given by (IV) vein
    Other Names:
  • Decadron
  • Outcome Measures

    Primary Outcome Measures

    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.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 25 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 (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:
    • Patients who meet any of the following criteria will be excluded from participation in the study:

    • 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 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 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center

    Investigators

    • Principal Investigator: David McCall, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT05645718
    Other Study ID Numbers:
    • 2022-0312
    • NCI-2022-10168
    First Posted:
    Dec 9, 2022
    Last Update Posted:
    Dec 27, 2022
    Last Verified:
    Dec 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 27, 2022