A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
NCT ID: NCT03677596
Last Updated: 2023-11-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
102 participants
INTERVENTIONAL
2019-07-01
2023-05-26
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
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).
TREATMENT
NONE
Study Groups
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Dose Level 2
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)
inotuzumab ozogamicin-dose level 2
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.
Dose Level 1
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)
Inotuzumab ozogamicin-dose level 1
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.
Interventions
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inotuzumab ozogamicin-dose level 2
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 1
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Have 1 or more of the following risk factors for developing VOD:
1. Due to receive Salvage 2 or greater;
2. Prior HSCT;
3. Age ≥55 years.
4. 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.
3. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy;
4. Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
5. Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment;
6. Age 18 years to 75 years;
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 2;
8. 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;
9. Serum creatinine ≤1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of \>=40 mL/min;
10. 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:
1. 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;
2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
3. Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
11. 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;
12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion Criteria
2. Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
3. 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;
4. Prior chemotherapy within 2 weeks before randomization with the following exceptions:
1. To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine;
2. For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors.
Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment.
5. Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization;
6. Prior inotuzumab ozogamicin treatment or other anti CD22 immunotherapy within 6 months before randomization;
7. 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;
8. 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);
9. 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);
10. 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;
11. Major surgery within 4 weeks before randomization;
12. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);
13. 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;
14. Patients with active heart disease or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;
15. QTcF \>470 msec (based on the average of 3 consecutive electrocardiogram \[ECGs\]);
16. Myocardial infarction within 6 months before randomization;
17. 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;
18. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia);
19. 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;
20. Administration of live vaccine within 6 weeks before randomization;
21. 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;
22. Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies;
23. 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;
24. 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;
25. 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);
26. 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.
18 Years
75 Years
ALL
No
Sponsors
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Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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Keck Hospital of USC
Los Angeles, California, United States
LAC+USC Medical Center
Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Maryland- Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
University of Washington Medical Center
Seattle, Washington, United States
Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia
Debrecen, , Hungary
Debreceni Egyetem Klinikai Központ, Pathológiai lntézet
Debrecen, , Hungary
Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
Nyíregyháza, , Hungary
Artemis hospital
Gurugram, Haryana, India
Sahyadri Clinical Research and Development Centre
Pune, Maharashtra, India
Sahyadri Super Speciality Hospital
Pune, Maharashtra, India
Sahyadri Super Speciality Hospital Nagar Road
Pune, Maharashtra, India
Sahyadri Super Speciality Hospital
Pune, Maharashtra, India
Christian Medical College
Vellore, Tamil Nadu, India
Christian Medical College Vellore- Ranipet Campus
Ranipet - 632517, Tamil Nadu, India, , India
Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne
Gdansk, , Poland
Instytut Hematologii i Transfuzjologii
Warsaw, , Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu
Wroclaw, , Poland
Apteka Centralna
Wroclaw, , Poland
National University Hospital
Singapore, , Singapore
Raffles Hospital
Singapore, , Singapore
Raffles Radiology
Singapore, , Singapore
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital General Universitario Gregorio Maranon
Madrid, , Spain
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Hospital General - Semisótano
Seville, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Hospital Universitari i Politecnic La Fe
Valencia, , Spain
Changhua Christian Hospital
Changhua, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Anadolu Health Center Hospital
Gebze, Istanbul, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center
Ankara, , Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department
Ankara, , Turkey (Türkiye)
Ankara University Faculty of Medicine Cebeci Hospital Hematology Department
Ankara, , Turkey (Türkiye)
Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center
Antalya, , Turkey (Türkiye)
Marmara University Pendik Training and Research Hospital Hematology Unit
Istanbul, , Turkey (Türkiye)
Ege University Medical Faculty
Izmir, , Turkey (Türkiye)
Dokuz Eylul University Medical Faculty
Izmir, , Turkey (Türkiye)
Medicalpark Izmir Hospital
Izmir, , Turkey (Türkiye)
Erciyes Universitesi Tip Fakultesi Hastaneleri
Kayseri, , Turkey (Türkiye)
Ondokuz Mayis University Faculty Of Medicine Hospital
Samsun, , Turkey (Türkiye)
Countries
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References
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Shi 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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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2018-001557-27
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
B1931030
Identifier Type: -
Identifier Source: org_study_id