LeukemiaPhase 4NCT03677596
A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
A Phase 4 study testing inotuzumab ozogamicin-dose level 2 and Inotuzumab ozogamicin-dose level 1 in people with Leukemia and Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, run by Pfizer at 45 sites in 8 countries.
Trial summary
This study will explore 2 different doses of inotuzumab ozogamicin including the dose that is approved and a lower dose. The main purpose of this study is to evaluate whether a dose of inotuzumab ozogamicin, lower than the approved dose, could be recommended for adult patient with relapsed or refractory ALL who may be… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC LEUKEMIA
- What is being tested?
- inotuzumab ozogamicin-dose level 2 and Inotuzumab ozogamicin-dose level 1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 45 sitesin 8 countries
- Study dates
- 1 Jul 2019to 26 May 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5% blasts) and who are eligible for HSCT;
- Have 1 or more of the following risk factors for developing VOD:
- Due to receive Salvage 2 or greater;
- Prior HSCT;
- Age ≥55 years.
- Ongoing or prior hepatic disease which may include a prior history of hepatitis or drug induced liver injury, as well as hepatic steatosis, nonalcoholic steatohepatitis, baseline elevations of bilirubin > upper limit of normal (ULN) and ≤1.5 x ULN.
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- Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy;
- Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
- Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment;
- Age 18 years to 75 years;
- Eastern Cooperative Oncology Group (ECOG) performance status 0 2;
- Adequate liver function, including total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN;
- Serum creatinine ≤1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >=40 mL/min;
- Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; patients with mental capacity which requires the presence of a legally authorized representative will be excluded from the study;
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Who cannot join
- Isolated extramedullary relapse (ie, testicular or central nervous system);
- Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
- Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion;
- Prior chemotherapy within 2 weeks before randomization with the following exceptions:
- To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine;
- For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors.
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- Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment.
- Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization;
- Prior inotuzumab ozogamicin treatment or other anti CD22 immunotherapy within 6 months before randomization;
- Prior allogeneic hematopoietic stem cell transplant (HSCT) within 90 days before randomization. Patients must have completed immunosuppression therapy for treatment of graft versus host disease (GvHD) prior to enrollment. At randomization, patients must not have Grade 2 or higher acute GvHD, or extensive chronic GvHD;
- Peripheral absolute lymphoblast count >=10,000 /L (treatment with hydroxyurea and/or steroids/vincristine is permitted within 2 weeks of randomization to reduce the white blood cell [WBC] count);
- Known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as human immunodeficiency virus [HIV] infection or severe inflammatory disease);
- Active hepatitis B infection as evidenced by hepatitis B surface antigen, active hepatitis C infection (must be anti-hepatitis C antibody negative or hepatitis C ribonucleic acid negative), or known seropositivity for HIV. HIV testing may need to be performed in accordance with local regulations or local practice;
- Major surgery within 4 weeks before randomization;
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);
- Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for >=2 years;
- Patients with active heart disease or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;
- QTcF >470 msec (based on the average of 3 consecutive electrocardiogram [ECGs]);
- Myocardial infarction within 6 months before randomization;
- History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of atrioventricular (AV) block unless a permanent pacemaker has been implanted;
- Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia);
- Prior confirmed or ongoing hepatic veno occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), or other serious or current ongoing liver disease such as cirrhosis or nodular regenerative hyperplasia;
- Administration of live vaccine within 6 weeks before randomization;
- Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia) or patients with a recent history (within 4 months) of deep tissue infections such as fascitis or osteomyelitis;
- Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies;
- Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of investigational product;
- Investigative site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study;
- Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation (up through the end of treatment visit);
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
Trial locations and contacts
45 sites in 8 countries.
45 sites in 8 countries
Turkey (Türkiye)11 sites
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center
Ankara, 06200
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department
Ankara, 06200
Ankara University Faculty of Medicine Cebeci Hospital Hematology Department
Ankara, 06590
Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center
Antalya, 07050
Anadolu Health Center Hospital
Gebze, Istanbul, 41400
Marmara University Pendik Training and Research Hospital Hematology Unit
Istanbul, 34899
Ege University Medical Faculty
Izmir, 35100
Dokuz Eylul University Medical Faculty
Izmir, 35340
Medicalpark Izmir Hospital
Izmir, 35575
Erciyes Universitesi Tip Fakultesi Hastaneleri
Kayseri, 38039
Ondokuz Mayis University Faculty Of Medicine Hospital
Samsun, 55200
Spain8 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
Hospital General - Semisótano
Seville, 41013
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Universitari i Politecnic La Fe
Valencia, 46026
United States7 sites
University of Maryland- Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Rush University Medical Center
Chicago, Illinois, 60612
Keck Hospital of USC
Los Angeles, California, 90033
LAC+USC Medical Center
Los Angeles, California, 90033
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Seattle Cancer Care Alliance
Seattle, Washington, 98109-1028
University of Washington Medical Center
Seattle, Washington, 98195
India7 sites
Artemis hospital
Gurugram, Haryana, 122001
Sahyadri Clinical Research and Development Centre
Pune, Maharashtra, 411004
Sahyadri Super Speciality Hospital
Pune, Maharashtra, 411004
Sahyadri Super Speciality Hospital Nagar Road
Pune, Maharashtra, 411006
Sahyadri Super Speciality Hospital
Pune, Maharashtra, 411006
Christian Medical College Vellore- Ranipet Campus
Ranipet - 632517, Tamil Nadu, India, 632517
Christian Medical College
Vellore, Tamil Nadu, 632004
Poland4 sites
Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214
Instytut Hematologii i Transfuzjologii
Warsaw, 02-776
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu
Wroclaw, 50-367
Apteka Centralna
Wroclaw, 50-556
Hungary3 sites
Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia
Debrecen, 4032
Debreceni Egyetem Klinikai Központ, Pathológiai lntézet
Debrecen, 4032
Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
Nyíregyháza, 4400
Singapore3 sites
National University Hospital
Singapore, 119074
Raffles Hospital
Singapore, 188770
Raffles Radiology
Singapore, 188770
Taiwan2 sites
Changhua Christian Hospital
Changhua, 500
National Taiwan University Hospital
Taipei, 10002
About this study
Official title: A PHASE 4, OPEN-LABEL, RANDOMIZED STUDY OF TWO INOTUZUMAB OZOGAMICIN DOSE LEVELS IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA ELIGIBLE FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION AND WHO HAVE RISK FACTOR(S) FOR VENO-OCCLUSIVE DISEASE
This study will explore 2 different doses of inotuzumab ozogamicin including the dose that is approved and a lower dose. The main purpose of this study is to evaluate whether a dose of inotuzumab ozogamicin, lower than the approved dose, could be recommended for adult patient with relapsed or refractory ALL who may be at higher risk for severe liver problems after inotuzumab ozogamicin treatment and stem cell transplant (a potentially curative therapy that can replace cancer cells with healthy cells). Efficacy and safety of the 2 doses will be evaluated.
- Being tested
- inotuzumab ozogamicin-dose level 2, Inotuzumab ozogamicin-dose level 1
- Keywords
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC leukemia, inotuzumab ozogamicin, Besponsa, transplant
- Medical subject headings
- Leukemia, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inotuzumab ozogamicin-dose level 2Drug
Also called Besponsa
Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose is 1.8mg/m2/cycle. This treatment arm evaluates a lower starting dose of 1.2mg/m2/cycle.
Inotuzumab ozogamicin-dose level 1Drug
Also called Besponsa
Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose of 1.8mg/m2/cycle is administered in this treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 2 | Experimental | Inotuzumab ozogamicin at starting dose 1.2 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days) Receives: Drug: inotuzumab ozogamicin-dose level 2 |
| Dose Level 1 | Active comparator | Inotuzumab ozogamicin at starting dose 1.8 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days) Receives: Drug: Inotuzumab ozogamicin-dose level 1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Veno-occlusive Disease (VOD)
VOD happened when the small blood vessels that lead into the liver and were inside the liver become blocked. VOD is defined as: a. Classical VOD (first 21 days after HSCT): Bilirubin>=2 mg/dL and 2 (or more) of the following criteria must also be present: 1. Painful hepatomegaly; 2. Weight gain >5%; 3. Ascites. b. Late onset VOD (>21 days after HSCT): Classical VOD beyond Day 21; or Histologically proven VOD; or Two or more of the following criteria must be present: 1. Bilirubin >2 mg/dL; 2. Painful hepatomegaly; 3. Weight gain >5%; 4. Ascites. and hemodynamical and/or ultrasound evidence of VOD.
Measured: 2 years from randomization
Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])
CR is defined as a disappearance of leukemia as indicated by<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC)>=1000/µL and platelets>=100000/µL. C1 extramedullary disease status is required. CRi is defined as CR except with ANC <1000/µL and/or platelets <100000/µL. C1 defined as complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions with following must be true: For participants with>= 1 measurable lesion, all nodal masses>1.5cm in greatest transverse diameter (GTD) at baseline (last assessment before 1st dose of study treatment) must must have regressed to>=1.5cm in GTD and all nodal masses>=1cm \& <=1.5cm in GTD at baseline have regressed to <1cm GTD or must have reduced by 75% in sum of products of greatest diameters. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Secondary outcomes (17)
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. On-treatment period was defined as the period starting with the 1st dose of study treatment through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All VOD cases were reported as SAE. Grades of severity were defined by Common terminology criteria for adverse events (CTCAE) v3.0. Grade 3=severe adverse event; Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related)
Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment emergent AEs (TEAEs) were defined as AEs that reported the period starting with the first dose of study treatment drug through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v3.0. Grade 3 = severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE. Causality of TEAEs were assessed by the Investigator. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)
A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All SAEs occurred after HSCT were reported in this OM. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: Starting from the first transplant after inotuzumab ozogamicin treatment and including the entire duration of subsequent follow up (approximately 52 weeks))
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Hematology (Activated partial thromboplastin time prolonged, Anemia, Hemoglobin increased, International normalization rate (INR) increased, Leukocytosis, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Chemistry (Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Chronic kidney disease, Creatinine increased, Gamma glutamyl transpeptidase (GGT) increased, Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia, Hypophosphatemia, Lipase increased and Serum amylase increased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity
MRD was assessed by flow cytometry for CD22 and other cell surface markers associated with B-cell ALL. In participants who achieved CR/CRi, MRD negativity was defined as defined as <1 abnormal cell/10^4 nucleated cells by flow cytometry per central laboratory analysis.
Measured: At screening, once at Day 16-28 of Cycles 1 and 2, or until CR/CRi and MRD negativity were achieved, then after every 1-2 cycles as clinically indicated, and at EOT visit (maximum of 2.5 years)
Duration of Remission (DoR) in Participants Achieving CR/CRi
DoR was defined as time from date of first response in responders (CR/CRi) to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments) or death due to any cause, whichever occurs first. DoR was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Progression-Free Survival
PFS was defined as time from date of randomization to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments), death due to any cause, or starting new induction therapy/post-therapy HSCT without achieving CR/CRi, whichever occured first. PFS was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Overall Survival
Overall survival was defined as the time from date of first dose of study treatment to death due to any cause. Participants without confirmation of death were censored at the date that the participant was last known to be alive. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment
Participants who underwent HSCT after inotuzumab ozogamicin treatment. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
The Cumulative Incidence Rate of Post-HSCT Relapse at Month 12
Post-HSCT relapse is defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to the date of first relapse post-HSCT. Cumulative incidence rates of an event at a particular timepoint were estimated with the CI calculated based on the cumulative incidence function using the method described by Kalbfleisch RL and Prentice JD. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment to Month 12
Number of Participants With Post-HSCT Mortality
Post-HSCT Mortality was defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participants With Post HSCT Non-Relapse Mortality
Post HSCT non-relapse mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause without prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participants With Post HSCT Relapse-Related Mortality
Post HSCT Relapse-Related Mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause with prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.
Measured: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin
Ctrough was defined as the mean Predose concentration of study treatment.
Measured: Pre-dose on Cycle 1 Day 1, 8 and 15, and on Day1 and 8 of Cycle 2, 3 and 4.
Number of Participants With Positive Anti-Drug Antibody (ADA)
ADA incidence is defined as combined results of treatment-boosted and treatment-induced ADA-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.
Measured: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Number of Participants With Positive Neutralizing Antibody (NAb)
NAb incidence is defined as combined results of treatment-boosted and treatment-induced NAb-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.
Measured: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start1 Jul 2019
- Primary completion21 Sep 2022
- Study completion26 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will be conducted in 2 phases: a run in phase and a randomized phase. Run in phase: a total of up to 22 patients will be enrolled to receive the starting dose of 1.2 mg/m2/cycle (dose level 2). A Simon Two Stage optimal design will be used. If acceptable efficacy (CR/CRi and MRD negativity) is observed in the run in phase, the study will enter the randomized phase. Randomized phase: if acceptable efficacy is observed in the run in phase, the study will enter the randomized phase. A total of approximately 80 patients will be randomized (1:1) to 1 of 2 dose levels of inotuzumab ozogamicin (40 patients per dose level).
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03677596
- Sponsor's protocol ID
- B1931030
- Other IDs
- 2018-001557-27, 2018
- Status last verified
- Oct 2023
- First submitted
- 27 Jul 2018
- Last updated
- 22 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Ozcan M, Cassaday RD, Zarzycka E, Vandendries E, Zhang F, Chen Y, Nieto A, Demirkan F, Montesinos P, Altuntas F. Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study. Haematologica. 2025 Aug 1;110(8):1736-1746. doi: 10.3324/haematol.2024.286091. Epub 2025 Jan 30.
PubMed 39882642Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
PubMed 35622074
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 4, OPEN-LABEL, RANDOMIZED STUDY OF TWO INOTUZUMAB OZOGAMICIN DOSE LEVELS IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA ELIGIBLE FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION AND WHO HAVE RISK FACTOR(S) FOR VENO-OCCLUSIVE DISEASE
- ClinicalTrials.gov ID
- NCT03677596
- Acronym / sponsor ID
- B1931030
- Keywords
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC leukemia, inotuzumab ozogamicin, Besponsa, transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 26 May 2023 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Posted 22 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will explore 2 different doses of inotuzumab ozogamicin including the dose that is approved and a lower dose. The main purpose of this study is to evaluate whether a dose of inotuzumab ozogamicin, lower than the approved dose, could be recommended for adult patient with relapsed or refractory ALL who may be at higher risk for severe liver problems after inotuzumab ozogamicin treatment and stem cell transplant (a potentially curative therapy that can replace cancer cells with healthy cells). Efficacy and safety of the 2 doses will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study will be conducted in 2 phases: a run in phase and a randomized phase. Run in phase: a total of up to 22 patients will be enrolled to receive the starting dose of 1.2 mg/m2/cycle (dose level 2). A Simon Two Stage optimal design will be used. If acceptable efficacy (CR/CRi and MRD negativity) is observed in the run in phase, the study will enter the randomized phase. Randomized phase: if acceptable efficacy is observed in the run in phase, the study will enter the randomized phase. A total of approximately 80 patients will be randomized (1:1) to 1 of 2 dose levels of inotuzumab ozogamicin (40 patients per dose level).
| Arm | Type | Receives |
|---|---|---|
| Dose Level 2 | Experimental | Drug: inotuzumab ozogamicin-dose level 2Inotuzumab ozogamicin at starting dose 1.2 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days) |
| Dose Level 1 | Active comparator | Drug: Inotuzumab ozogamicin-dose level 1Inotuzumab ozogamicin at starting dose 1.8 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5% blasts) and who are eligible for HSCT;
- Have 1 or more of the following risk factors for developing VOD:
- Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy;
- Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
- Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment;
Key exclusion criteria (29 listed)
- Isolated extramedullary relapse (ie, testicular or central nervous system);
- Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
- Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion;
- Prior chemotherapy within 2 weeks before randomization with the following exceptions:
- Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inotuzumab ozogamicin-dose level 2Also: BesponsaInotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose is 1.8mg/m2/cycle. This treatment arm evaluates a lower starting dose of 1.2mg/m2/cycle. | Drug | Dose Level 2 |
| Inotuzumab ozogamicin-dose level 1Also: BesponsaInotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose of 1.8mg/m2/cycle is administered in this treatment arm. | Drug | Dose Level 1 |
Primary outcome
Percentage of Participants With Veno-occlusive Disease (VOD)
Time frame: 2 years from randomization
VOD happened when the small blood vessels that lead into the liver and were inside the liver become blocked. VOD is defined as: a. Classical VOD (first 21 days after HSCT): Bilirubin>=2 mg/dL and 2 (or more) of the following criteria must also be present: 1. Painful hepatomegaly; 2. Weight gain >5%; 3. Ascites. b. Late onset VOD (>21 days after HSCT): Classical VOD beyond Day 21; or Histologically proven VOD; or Two or more of the following criteria must be present: 1. Bilirubin >2 mg/dL; 2. Painful hepatomegaly; 3. Weight gain >5%; 4. Ascites. and hemodynamical and/or ultrasound evidence of VOD.
Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
CR is defined as a disappearance of leukemia as indicated by<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC)>=1000/µL and platelets>=100000/µL. C1 extramedullary disease status is required. CRi is defined as CR except with ANC <1000/µL and/or platelets <100000/µL. C1 defined as complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions with following must be true: For participants with>= 1 measurable lesion, all nodal masses>1.5cm in greatest transverse diameter (GTD) at baseline (last assessment before 1st dose of study treatment) must must have regressed to>=1.5cm in GTD and all nodal masses>=1cm \& <=1.5cm in GTD at baseline have regressed to <1cm GTD or must have reduced by 75% in sum of products of greatest diameters. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable.
17 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related)
Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)
Time frame: Starting from the first transplant after inotuzumab ozogamicin treatment and including the entire duration of subsequent follow up (approximately 52 weeks))
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity
Time frame: At screening, once at Day 16-28 of Cycles 1 and 2, or until CR/CRi and MRD negativity were achieved, then after every 1-2 cycles as clinically indicated, and at EOT visit (maximum of 2.5 years)
Duration of Remission (DoR) in Participants Achieving CR/CRi
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Progression-Free Survival
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Overall Survival
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
The Cumulative Incidence Rate of Post-HSCT Relapse at Month 12
Time frame: From first dose of study treatment to Month 12
Number of Participants With Post-HSCT Mortality
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participants With Post HSCT Non-Relapse Mortality
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Number of Participants With Post HSCT Relapse-Related Mortality
Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin
Time frame: Pre-dose on Cycle 1 Day 1, 8 and 15, and on Day1 and 8 of Cycle 2, 3 and 4.
Number of Participants With Positive Anti-Drug Antibody (ADA)
Time frame: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Number of Participants With Positive Neutralizing Antibody (NAb)
Time frame: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39882642Ozcan M, Cassaday RD, Zarzycka E, Vandendries E, Zhang F, Chen Y, Nieto A, Demirkan F, Montesinos P, Altuntas F. Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study. Haematologica. 2025 Aug 1;110(8):1736-1746. doi: 10.3324/haematol.2024.286091. Epub 2025 Jan 30.
- Derived from this study: PubMed 35622074Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
45 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing inotuzumab ozogamicin-dose level 2 and Inotuzumab ozogamicin-dose level 1 in people with Leukemia and Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, run by Pfizer at 45 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in Turkey (Türkiye), Spain, United States, India, Poland and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Veno-occlusive Disease (VOD) (time frame: 2 years from randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03677596, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.