Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

After preconditioning with chemotherapy, IM83 CAR-T Cells will be evaluated

IM83 CAR-T Cells, 5×10\^8 cells, 1×10\^9 cells, and 2×10\^9 cells, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 30 mg/m\^2 (D-5\~D- 3), determined by tumor burden at baseline. Drug: Fludarabine Recommendation: 30 mg/m\^2 (D-5\~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m\^2 (D-5\~D-3), determined by tumor burden at baseline.

IM83 CAR-T Cells

Yu Zhang, PhD

Junhua Nie, PhD

The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma

This study is planned to enroll 9-18 patients with relapsed or refractory osteosarcoma in a modified "3+3" design for dose escalation, with three dose groups of 5×10\^8 cells, 1×10\^9 cells, and 2×10\^9 cells.3-6 subjects are planned to be enrolled in each dose group to assess their safety. Each dose group is planned to enroll 3-6 subjects to assess safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in a dose group, the transfusion of cells from the next dose group can be initiated.

This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.

IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma

Phase I Clinical Study to Evaluate the Safety and Efficacy of IM83 CAR-T Cells for the Treatment of Relapsed or Refractory Osteosarcoma

Incidence of Adverse Events and Abnormal Findings on Clinically Significant Laboratory Tests Associated with IM83 CAR-T Cell Therapy Within 28 Days of Infusion

Objective remission rate (ORR) after infusion

Duration of disease remission (DoR) after infusion

Progress free survival (PFS) after infusion

AUC 0-D28 of IM83 CAR-T cells in vivo (peripheral blood) after infusion

AUC 0-D90 of IM83 CAR-T cells in vivo (peripheral blood) after infusion

Peak Concentrationof IM83 CAR-T cells in vivo (peripheral blood) after infusion

Guangdong Provincial People's Hospital

Beijing Immunochina Medical Science & Technology Co., Ltd.

Etoposide

Lenvatinib

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

Enzyme Inhibitors

Protein Kinase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.

Participants with relapsed or refractory osteosarcoma will receive ifosfamide with etoposide. Participants with relapsed or refractory osteosarcoma may receive optional lenvatinib plus or minus chemotherapy (Ifosfamide and Etoposide) if disease progression is observed in study.

Lenvatinib 14 milligrams per square meter (mg/m\^2) capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until disease progression (PD), development of unacceptable toxicity, participant request, withdrawal of consent, or discontinuation of study by the sponsor.

An extemporaneous suspension of lenvatinib capsules may be used for participants unable to swallow capsules.

Ifosfamide 3000 milligrams per square meter per day (mg/m\^2/day) intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.

Etoposide 100 mg/m\^2/day intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.

Lenvatinib 14 mg/m\^2 capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until the next PD (per response evaluation criteria in solid tumors \[RECIST\] 1.1 as assessed by investigator), development of unacceptable toxicity, participant request, or withdrawal of consent, whichever occurs first.

This Is a Multicenter, Randomized, Open-Label, Parallel-Group, Phase 2 Study to Compare the Efficacy and Safety of Lenvatinib in Combination with Ifosfamide and Etoposide Versus Ifosfamide and Etoposide in Children, Adolescents, and Young Adults with Relapsed or Refractory Osteosarcoma.

A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma

A Multicenter, Open-label, Randomized Phase 2 Study to Compare the Efficacy and Safety of Lenvatinib in Combination With Ifosfamide and Etoposide Versus Ifosfamide and Etoposide in Children, Adolescents and Young Adults With Relapsed or Refractory Osteosarcoma (OLIE)

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

PFS as assessed by IIR was defined as the time from the date of randomization to the date of the first documentation of PD or date of death (whichever occurred first), as determined using RECIST v1.1. PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier method.

PFS rate at 4 months as assessed by IIR was defined as the percentage of participants who were alive and without PD at 4 months from the randomization date using RECIST v1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. The PFS-4m was estimated using the Kaplan-Meier method. Final analysis data was reported for this outcome measure.

PFS-1y rate as assessed by IIR was defined as the percentage of participants who were alive and without PD at 1 year from randomization date using RECIST v1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS-1y rate was estimated using Kaplan-Meier method. Final analysis data was reported for this outcome measure.

OS is defined as the time from the date of randomization to the date of death from any cause. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2025).

OS-1y was defined as the time from the date of randomization to the date of death from any cause assessed up to 1 year. OS was calculated using the Kaplan-Meier method. Final analysis data was reported for this outcome measure.

ORR-4m was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) as determined by IIR using RECIST v1.1 within the first 4 months. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 95% confidence interval (CI) of ORR was calculated using the method of Clopper and Pearson. Final analysis data was reported for this outcome measure.

ORR by IIR was defined as the percentage of participants with best overall response of CR or PR determined using RECIST v1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 95% CI of ORR was calculated using the method of Clopper and Pearson. Final analysis data was reported for this outcome measure.

TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria. Data for this outcome measure will be reported after study completion (anticipated study completion date is March 2025).

Plasma concentration of lenvatinib in participants from Treatment Arm A (Lenvatinib + Ifosfamide + Etoposide) at different time points were reported. As planned, data for this outcome measure was analyzed for treatment arm A only. Lenvatinib concentration in plasma was quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Final analysis data was reported for this outcome measure.

Health-Related Quality of Life (HRQoL): PedsQL 4.0 Generic Core Scale is a multidimensional scale. It included assessment of 4 dimensions: physical functioning (8 items), emotional functioning (8 items), social functioning (8 items), and school functioning (5 items - children greater than or equal to \[\>=\] 5 years, adults; 3 items - toddlers \[aged 2-4 years\]). Each item was reported using a 5-point Likert scale, items were then reverse-scored and linearly transformed to a 0 to 100 scale. Generic Core Scale total score: sum of all the items divided by the number of items answered across all the scales. Total score ranges from 0 to 100, where higher scores=better HRQoL, lower scores=worse HRQoL. Final analysis data was reported for this outcome measure.

HRQoL: PedsQL 3.0 Cancer Module Scale measured pediatric cancer-specific HRQoL. It included assessment of 8 dimensions: pain and hurt (2 items), nausea (5 items), procedural anxiety (3 items), treatment anxiety (3 items), worry (3 items), cognitive problems (3 items - toddlers \[aged 2-4\], 4 items - young children \[aged 5-7\]; 5 items for children aged \>=8 years, adults), perceived physical appearance (3 items), communication (3 items). Each item was reported using a 5-point Likert scale, items were then reverse-scored and linearly transformed to a 0 to 100 scale. Cancer Module total score: sum of all items divided by the number of items answered on all the scales. Total score ranges from 0 to 100, where higher scores=better HRQoL, lower scores=worse HRQoL. Final analysis data was reported for this outcome measure.

The palatability and acceptability of lenvatinib oral suspension formulation was assessed using the Palatability Questionnaire. In the questionnaire, participants were asked to answer palatability and acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell, how does it feel in the mouth and overall acceptability in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. In this outcome measure, number of participants have been reported per their overall palatability and acceptability responses. Final analysis data was reported for this outcome measure.

Merck Sharp & Dohme LLC

Eisai Inc.

All-Cause Mortality: FAS included all randomized participants regardless of the treatment actually received. Serious and Other Adverse Events: Safety Analysis Set included participants who received at least 1 dose of any study drug. Treatment Arm B safety data for Ifosfamide + Etoposide to Lenvatinib (optional) were reported separately.

Participants received lenvatinib 14 mg/m\^2, capsules, orally, once daily, plus ifosfamide 3000 mg/m\^2/day, intravenously and etoposide 100 mg/m\^2/day, intravenously. Ifosfamide and etoposide were administered on Days 1 to 3 of each 21-day cycle for up to 5 cycles. Lenvatinib was administered in continuous 21-day cycles. Treatment continued until PD, development of unacceptable toxicity, participant choice, withdrawal of consent or discontinuation of study by the sponsor, whichever occurred first.

Treatment Arm A: Lenvatinib + Ifosfamide + Etoposide

Participants received ifosfamide 3000 mg/m\^2/day, intravenously and etoposide 100 mg/m\^2/day, intravenously on Days 1 to 3 of each 21-day cycle for up to 5 cycles. Participants who had PD per RECIST v1.1 were eligible for an optional lenvatinib treatment (14 mg/m\^2, capsules, orally, once daily in continuous 21-day cycles until next PD, development of unacceptable toxicity, participant choice, withdrawal of consent or discontinuation of study by the sponsor, whichever occurred first) plus any remaining cycles of chemotherapy if 5 cycles were not completed prior to PD.

Treatment Arm B: Ifosfamide + Etoposide

Eligible participants from Treatment Arm B: Ifosfamide+Etoposide who had PD per RECIST v1.1 received an optional lenvatinib treatment (14 mg/m\^2, capsules, orally, once daily in continuous 21-day cycles until next PD, development of unacceptable toxicity, participant choice, withdrawal of consent or discontinuation of study by the sponsor, whichever occurred first) plus any remaining cycles of chemotherapy if 5 cycles were not completed prior to PD.

Treatment Arm B: Ifosfamide+Etoposide to Lenvatinib (Optional)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

American Indian or Alaskan Native

Other

Missing

Race/Ethnicity, Customized

Full Analysis Set (FAS) included all randomized participants regardless of the treatment actually received.

Eisai Medical Information

FAS included all randomized participants regardless of the treatment actually received.

Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment

Percentage of Participants With PFS at Month 4 (PFS-4m Rate) by IIR Assessment

Percentage of Participants With PFS at 1 Year or Month 12 (PFS-1y Rate) by IIR Assessment

Overall Survival (OS)

Percentage of Participants With Overall Survival at 1 Year or Month 12 (OS-1y)

Objective Response Rate at Month 4 (ORR-4m) by IIR Assessment

ORR by IIR Assessment

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

Cycle 1, Day 1: 0.5-4 hours post-dose

Cycle 1, Day 1: 6-10 hours post-dose

Cycle 1, Day 15: Pre-dose

Cycle 1, Day 15: 0.5-4 hours post-dose

Cycle 1, Day 15: 6-10 hours post-dose

Cycle 2, Day 1: Pre-dose

Population Pharmacokinetic (PK) Analysis Set included those participants who received at least 1 dose of lenvatinib and had documented dose administration history and measurable plasma concentrations of lenvatinib. Here "overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure. Here "number analyzed, n" signifies participants who were evaluable for this outcome measure at given time points.

Treatment Arm A: Plasma Concentration of Lenvatinib

HRQoL Analysis Set included all participants who had received at least 1 dose of study drug and had completed at least 1 postbaseline patient-reported outcome (PRO) assessment. Here "overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scale: Generic Core Scale Score at Month 4

HRQoL Analysis Set included all participants who had received at least 1 dose of study drug and had completed at least 1 postbaseline PRO assessment. Here "overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Change From Baseline in PedsQL Scale: Cancer Module Scale Score at Month 4

Super Bad

Really Bad

May be Good or May be Bad

Good

Really Good

Super Good

Participants received lenvatinib 14 mg/m\^2 suspension, orally, once daily in continuous 21-day cycles until PD, development of unacceptable toxicity, participant request, withdrawal of consent, or discontinuation of study by the sponsor. Participants who were unable to swallow capsules received lenvatinib as an extemporaneous suspension prepared from the capsule.

All Participants: Lenvatinib 14 mg/m^2

Palatability and acceptability analysis set included all participants who received oral suspension of lenvatinib in Treatment Arm A and who received an optional lenvatinib suspension in Treatment Arm B and who answered at least 1 question in the palatability questionnaire. As planned, combined data for Lenvatinib from Treatment Arm A and B was reported for this outcome measure. Here "overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Number of Participants Categorized Based on Overall Palatability and Acceptability Questionnaire Responses for Suspension of Lenvatinib

Participants received lenvatinib 14 milligrams per square meter (mg/m\^2), capsules, orally, once daily, plus ifosfamide 3000 milligrams per square meter per day (mg/m\^2/day), intravenously and etoposide 100 mg/m\^2/day, intravenously. Ifosfamide and etoposide were administered on Days 1 to 3 of each 21-day cycle for up to 5 cycles. Lenvatinib was administered in continuous 21-day cycles. Treatment continued until disease progression (PD), development of unacceptable toxicity, participant choice, withdrawal of consent or discontinuation of study by the sponsor, whichever occurred first.

Participants received ifosfamide 3000 mg/m\^2/day, intravenously and etoposide 100 mg/m\^2/day, intravenously on Days 1 to 3 of each 21-day cycle for up to 5 cycles. Participants who had PD per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 were eligible for an optional lenvatinib treatment (14 mg/m\^2, capsules, orally, once daily in continuous 21-day cycles until next PD, development of unacceptable toxicity, participant choice, withdrawal of consent or discontinuation of study by the sponsor, whichever occurred first) plus any remaining cycles of chemotherapy if 5 cycles were not completed prior to PD.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma	NCT06412458	Refractory Oste... Recurrent Osteo...	IM83 CAR-T Cell...	16 Years -	Beijing Immunochina Medical Science & Technology Co., Ltd.
A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma	NCT04154189	Osteosarcoma	Lenvatinib Ifosfamide Etoposide Lenvatinib	2 Years - 25 Years	Eisai Inc.
A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma	NCT04154189	Osteosarcoma	Lenvatinib Ifosfamide Etoposide Lenvatinib	2 Years - 25 Years	Eisai Inc.
IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma	NCT06412458	Refractory Oste... Recurrent Osteo...	IM83 CAR-T Cell...	16 Years -	Beijing Immunochina Medical Science & Technology Co., Ltd.
A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma	NCT04154189	Osteosarcoma	Lenvatinib Ifosfamide Etoposide Lenvatinib	2 Years - 25 Years	Eisai Inc.

Spots Global Cancer Trial Database for relapsed or refractory osteosarcoma