Intravenous Ixazomib in Pediatric Participants With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LLy)

NCT03888534 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: C16051U1111-1225-35282018-003907-20
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), safety and toxicity, and pharmacokinetics (PK) of ixazomib administered intravenously in combination with multiagent reinduction chemotherapy in pediatric participants with relapsed/refractory ALL or LLy.

Conditions

Precursor Cell Lymphoblastic Leukemia-lymphoma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Number of Participants with Dose-limiting Toxicities (DLT) During Reinduction Chemotherapy

  DLT: Grade 4 nonhematologic toxicity after first dose of ixazomib and is probably/definitely attributable to the ixazomib treatment regimen, with exceptions, example fever/infection with/without hospitalization, fatigue and gastrointestinal symptoms, hypofibrinogenemia, metabolic/laboratory abnormalities that resolve to less than or equal to(\<=)Grade 2 within 7 days. Any Grade 3/4 nonhematologic toxicity after first dose of ixazomib that is possibly/probably/definitely attributable to the ixazomib treatment regimen and results in omission of subsequent dose of chemotherapy, with exception of fever/infection. Hematologic toxicities: Failure to recover a peripheral absolute neutrophil count (ANC) ≥0.5\*10\^9 per liter (/L) and a platelet count ≥50\*10\^9/L due to documented bone marrow hypoplasia (cellularity \<10 20%) within 42 days after the beginning of systemic chemotherapy without evidence of active disease by bone marrow evaluation or active infection.

  Up to Day 29

• Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  Up to 30 months

• Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Clinical Laboratory Parameters

  Up to 30 months

• AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for Ixazomib

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose and Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration for Ixazomib

  Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose and Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

Secondary Outcomes (1)

• Overall Response Rate (ORR)

  Up to 30 months

Study Arms (1)

Ixazomib

EXPERIMENTAL

Ixazomib, injection, intravenously, once on Days 1, 4, 8, and 11 in a single 29-day treatment cycle in combination with multiagent reinduction therapy. Participants \>= 1 year will receive the starting dose of 1.0 milligram per square meter (mg/m\^2) and \<1 year will receive the starting dose of 0.03 milligram per kilogram (mg/kg). The dose escalation phase will determine the MTD or RP2D of Ixazomib. Dose of Ixazomib will be escalated based on the observed safety and tolerability data.

Drug: Ixazomib

Interventions

Ixazomib DRUG

Ixazomib intravenous injection in combination with reduction chemotherapy.

Also known as: MLN9708

Ixazomib

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of relapsed/refractory ALL with or without extramedullary disease, including central nervous system (CNS)2 (\<5 white blood cell \[WBC\]/mcL\] in the cerebrospinal fluid \[CSF\] with blasts) and CNS3 (\>=5 WBC/mcL in the CSF with blasts), or relapsed/refractory LLy. Participants with mixed-phenotype ALL or mature (Burkitt-like) leukemia are excluded.
• Relapsed/refractory ALL must have \>=5% blasts in the bone marrow by morphology.
• Relapsed/refractory LLy participants must have measurable disease documented by clinical, radiologic, and histologic criteria.
• A Karnofsky performance status of \>=50% (for participants aged \>16 years) and a Lansky performance status of \>=50% (for participants aged \<=16 years).
• Adequate organ function.
• Failure of 1 or more therapeutic attempts.
• Full recovery from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before entering this study, as follows:
• Cytoreduction with hydroxyurea: Hydroxyurea can be initiated and continued for up to 24 hours before the start of protocol therapy.
• Cytotoxic therapy: At least 14 days must have elapsed since the completion of the last dose of chemotherapy, except intrathecal (IT) chemotherapy and/or maintenance therapy, such as vincristine (VCR), mercaptopurine, methotrexate, or glucocorticoids. There is no waiting period for those relapsing on maintenance therapy.
• Hematopoietic stem cell transplantation (HSCT): Participants who have relapsed after HSCT are eligible, provided they have no evidence of acute or chronic graft-versus-host disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days posttransplant at the time of enrollment.
• Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with granulocyte colony-stimulating factor (G-CSF) or other growth factor at the time of enrollment. At least 14 days must have elapsed since the completion of therapy with pegfilgrastim.
• Biologic (antineoplastic agent): At least 7 days must have elapsed since the last dose of a biologic agent. For agents that have known adverse events (AEs) occurring beyond 7 days after the end of administration, this period must be extended beyond the time during which AE are known to occur. The duration of this interval must be approved by the project clinician (or designee).
• Monoclonal antibodies: At least 3 half-lives must have elapsed after the last dose of an administered monoclonal antibody.
• Immunotherapy: At least 30 days must have elapsed after the completion of any type of immunotherapy (example, tumor vaccines, chimeric antigen receptor T-cells).
• Photon radiotherapy (XRT): Craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to any extramedullary site other than the CNS; \>=90 days must have elapsed if prior total body irradiation or craniospinal XRT was given.

You may not qualify if:

• ALL participants: have isolated extramedullary disease, including CNS or testicular disease.
• Have Grade \>=2 peripheral sensory or motor neuropathy, defined by the Modified "Balis" Pediatric Scale of Pediatric Neuropathies, at the time of enrollment.
• Have a planned administration of chemotherapy, radiation therapy, or immunotherapy, other than the study drugs used for this protocol.
• Have deoxyribonucleic acid fragility syndromes (example, Fanconi anemia, Bloom syndrome).
• Have Down syndrome.
• Are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus host disease (GVHD) after HSCT.
• Have Philadelphia chromosome (Ph)-positive ALL or Ph-like ALL and are currently receiving tyrosine kinase inhibitor therapy.
• Are receiving systemic treatment with strong inducers of cytochrome P450 3A (CYP3A)(example,rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) within 14 days before study enrollment.
• Are receiving systemic treatment with strong CYP3A inhibitors within 14 days before study enrollment.
• Are receiving systemic treatment with inhibitors or inducers of P-glycoprotein (P-gp) within 14 days before study enrollment.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 8035, Spain

Location

C.H. Regional Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: March 25, 2019
• Study Start: October 31, 2020
• Primary Completion: August 30, 2022
• Study Completion: August 30, 2022
• Last Updated: September 28, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

US (4); ES (3)