TriangleNCT01564784 · CITED IN SOURCE DOCUMENTS
A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2019-01-09
This study will compare the efficacy, in terms of complete responses and overall survival, of inotuzumab ozogamicin versus investigator's choice of chemotherapy.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
Overall Survival (OS)
Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
Progression-Free Survival (PFS)
Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
Change From Baseline in EQ-5D VAS
Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * CD22 expression * Adequate liver and renal functions Exclusion Criteria: * Isolated extramedullary disease * Active Central Nervous System \[CNS\] disease
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: inotuzumab ozogamicin
- label
- Arm A
- type
- EXPERIMENTAL
- intervention Names
- Drug: FLAG (fludarabine, cytarabine and G-CSF)
- Drug: HIDAC (high dose cytarabine)
- Drug: cytarabine and mitoxantrone
- label
- Arm B
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Arm A
- description
- Dose: inotuzumab ozogamicin 0.8-0.5 mg/m\^2 IV, weekly, 3 times per cycle Cycle length: 21-28 days Total number of cycles: 6
- name
- inotuzumab ozogamicin
- type
- DRUG
- arm Group Labels
- Arm B
- description
- Dose: cytarabine 2.0 g/m\^2/day IV days 1-6 fludarabine30 mg/m\^2/day IV days 2-6 Cycle length: 28 days Total number of cycles: 4
- name
- FLAG (fludarabine, cytarabine and G-CSF)
- type
- DRUG
- arm Group Labels
- Arm B
- description
- cytarabine 3 g/m\^2 IV every 12 hours for up to 12 times
- name
- HIDAC (high dose cytarabine)
- type
- DRUG
- arm Group Labels
- Arm B
- description
- mitoxantrone 12 mg/m\^2 IV days 1-3 cytarabine 200 mg/m\^2/day IV over 7 days cycle length: 15-20 days Total number of cycles: 4
- name
- cytarabine and mitoxantrone
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 326
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- CR was the disappearance of leukemia indicated by less than (\<) 5 percent (%) marrow blasts \& absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) \& platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable \& non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (\>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm \& ≤1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen \& other previously enlarged organs must have regressed in size \& must not be palpable) was required. CRi was defined as CR except ANC \<1000/μL \&/or platelets \<100,000/μL.
- measure
- Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
- time Frame
- Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose
- description
- OS was defined as the time from randomization to date of death due to any cause. Participants last known to be alive were censored at date of last contact.
- measure
- Overall Survival (OS)
- time Frame
- Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.
- secondary Outcomes
- description
- DoR was defined as time from date of first response in responders (CR/CRi per Investigator assessment) to date of PFS event (i.e. death, progressive disease \[objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status\] or starting new induction therapy or post-therapy stem cell transplant \[SCT\] without achieving CR/CRi). Responders without PFS events were censored at the last valid disease assessment including follow-up.
- measure
- Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
- time Frame
- Up to 2 years from randomization
- description
- PFS was defined as time from date of randomization to earliest date of the following events: death, progressive disease (objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status) and starting new induction therapy or post-therapy SCT without achieving CR/CRi. Participants without a PFS event at time of analysis were censored at the last valid disease assessment. In addition, participants with documentation of an event after an unacceptably long interval (\>28 weeks if there was post-baseline disease assessment, or \>12 weeks if there was no post-baseline assessment) since the previous disease assessment were censored at the time of the previous assessment (date of randomization if no post-baseline assessment). Post-study treatment follow-up disease assessments was included. Kaplan-Meier method used and 2-sided 95% confidence interval (CI) calculated based on the Brookmeyer and Crowley method.
- measure
- Progression-Free Survival (PFS)
- time Frame
- Up to 2 years from randomization
- description
- HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.
- measure
- Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
- time Frame
- Up to 19 weeks from last dose
- description
- MRD analysis was performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study, were sent to the central laboratory and analyzed using multiparametric flow cytometry. The antibody combinations were designed to maximize discrimination between normal and abnormal cells of B-cell lineage and similar maturational stage and included antibodies detecting cluster of differentiation (CD) 9, CD10, CD13, CD19, CD20, CD33, CD34, CD38, CD45, CD58, CD66c, and CD123. A peripheral blood sample was provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity was considered to have been achieved if the lowest value of MRD from the first date of CR/CRi to EoT was \<1 × 10\^-4 blasts/nucleated cells.
- measure
- Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
- time Frame
- Up to approximately 4 weeks (EoT) from last dose of study drug
- description
- Karyotyping was required locally, at screening and at least once during the study in participants who had abnormal cytogenetics at baseline and who achieved CR/CRi. Data presented below are for participants who achieved CR/CRi per EAC and had abnormal karyotype at screening.
- measure
- Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
- time Frame
- Up to approximately 4 weeks (EoT) from last dose of study drug
- description
- Blood samples were collected and analyzed for inotuzumab ozogamicin serum concentrations using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) method with a lower limit of quantification of 1.0 nanograms per milliliter (ng/mL). Cmax was the maximum observed concentration occurring between 0-8 hours post-dose. Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours. n = number of observations (non-missing concentrations).
- measure
- Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
- time Frame
- Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4
- description
- This questionnaire comprised 30 questions within which are 9 multi-item scales \& 6 single-item measures. There are 5 functional scales; physical, role, cognitive, emotional \& social, 3 symptom scales; fatigue, pain, \& nausea \& vomiting, \& a global health status/quality of life (QoL) scale. There are 5 single item measures assessing additional symptoms commonly reported by cancer patients (loss of appetite, insomnia, constipation, diarrhea, \& dyspnea) \& a single item concerning perceived financial impact of the disease. Most questions used a 4 point scale (1='not at all' to 4='very much'); 2 questions used a 7-point scale (1='very poor' to 7='excellent'). Scores were averaged \& transformed to a scale ranging from 0 to 100; a higher score indicates a better level of functioning or greater degree of symptoms.
- measure
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
- time Frame
- Day 1 of each cycle prior to dosing and EoT
- description
- The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no problems", "some problems", and "extreme problems". The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).
- measure
- Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
- time Frame
- Day 1 of each cycle prior to dosing and EoT
- description
- The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no problems", "some problems", and "extreme problems". The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
- measure
- Change From Baseline in EQ-5D VAS
- time Frame
- Day 1 of each cycle prior to dosing and EoT
- description
- VOD/SOS was defined as the occurrence of 2 out of the following 3 clinical criteria: 1) total serum bilirubin level \>34 micromoles per liter (μmol/L) (\>2.0 milligrams per deciliter \[mg/dL\]), 2) an increase in liver size from baseline or development of right upper quadrant pain of liver origin and 3) sudden weight gain \>2.5% (eg, within a 72 hour period) because of fluid accumulation in the weeks following infusion of study drug or chemotherapy, or HSCT conditioning/preparative therapy, or development of ascites not present at baseline following such exposures AND the absence of other explanations for these signs and symptoms, OR development of bilirubin elevation, weight gain, or hepatomegaly plus histologic abnormalities on liver biopsy demonstrating hepatocyte necrosis in zone 3 of the liver acinus, sinusoidal fibrosis, and centrilobular hemorrhage, with or without fibrosis of the terminal hepatic venules.
- measure
- Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
- time Frame
- Up to 2 years from randomization
Full study description
- brief Summary
- This study will compare the efficacy, in terms of complete responses and overall survival, of inotuzumab ozogamicin versus investigator's choice of chemotherapy.
Source references
- references
- citation
- Zhao Y, Laird AD, Roberts KG, Yafawi R, Kantarjian H, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gokbuget N, O'Brien S, Jabbour E, Cassaday RD, Loyd MR, Olsen S, Neale G, Liu X, Vandendries E, Advani A, Mullighan CG. Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL. Blood Adv. 2024 Jun 25;8(12):3226-3236. doi: 10.1182/bloodadvances.2023012430.
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- pmid
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- citation
- Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.
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Source notices and limitations
Discovery and provenance
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- 14. CLINICAL STUDIES Relapsed or Refractory ALL INO-VATE ALL Study – Adult Patients The safety and efficacy of BESPONSA were evaluated in INO-VATE ALL (NCT01564784) a randomized (1:1), open‑label, international, multicenter study in patients with relapsed or refractory ALL. Patients were stratified at randomization based
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Preserved source evidence · Not medical advice