A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

NCT03677596 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: B19310302018-001557-27
• Study Type: interventional
• Target: 102
• Locations: 8 countries
• Sites: 45

Brief 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 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.

Conditions

Leukemia; Precursor b-Cell Lymphoblastic Leukemia-Lymphoma; ACUTE LYMPHOBLASTIC LEUKEMIA

Keywords

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; ACUTE LYMPHOBLASTIC leukemia; inotuzumab ozogamicin; Besponsa; transplant

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  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)

  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

  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

  From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

Study Arms (2)

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)

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)

Drug: Inotuzumab ozogamicin-dose level 1

Interventions

inotuzumab ozogamicin-dose level 2 DRUG

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.

Also known as: Besponsa

Dose Level 2

Inotuzumab ozogamicin-dose level 1 DRUG

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.

Also known as: Besponsa

Dose Level 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;

You may not qualify if:

• Isolated extramedullary relapse (ie, testicular or central nervous system);
• Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
• 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.
• 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;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (45)

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Maryland- Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1028, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia

Debrecen, 4032, Hungary

Location

Debreceni Egyetem Klinikai Központ, Pathológiai lntézet

Debrecen, 4032, Hungary

Location

Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia

Nyíregyháza, 4400, Hungary

Location

Artemis hospital

Gurugram, Haryana, 122001, India

Location

Sahyadri Clinical Research and Development Centre

Pune, Maharashtra, 411004, India

Location

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411004, India

Location

Sahyadri Super Speciality Hospital Nagar Road

Pune, Maharashtra, 411006, India

Location

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411006, India

Location

Christian Medical College

Vellore, Tamil Nadu, 632004, India

Location

Christian Medical College Vellore- Ranipet Campus

Ranipet - 632517, Tamil Nadu, India, 632517, India

Location

Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu

Wroclaw, 50-367, Poland

Location

Apteka Centralna

Wroclaw, 50-556, Poland

Location

National University Hospital

Singapore, 119074, Singapore

Location

Raffles Hospital

Singapore, 188770, Singapore

Location

Raffles Radiology

Singapore, 188770, Singapore

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital General - Semisótano

Seville, 41013, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Anadolu Health Center Hospital

Gebze, Istanbul, 41400, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center

Ankara, 06200, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department

Ankara, 06200, Turkey (Türkiye)

Location

Ankara University Faculty of Medicine Cebeci Hospital Hematology Department

Ankara, 06590, Turkey (Türkiye)

Location

Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center

Antalya, 07050, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital Hematology Unit

Istanbul, 34899, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Dokuz Eylul University Medical Faculty

Izmir, 35340, Turkey (Türkiye)

Location

Medicalpark Izmir Hospital

Izmir, 35575, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi Hastaneleri

Kayseri, 38039, Turkey (Türkiye)

Location

Ondokuz Mayis University Faculty Of Medicine Hospital

Samsun, 55200, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 35622074 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Leukemia; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: September 19, 2018
• Study Start: July 1, 2019
• Primary Completion: September 21, 2022
• Study Completion: May 26, 2023
• Last Updated: November 22, 2023
• Results First Posted: November 22, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

TW (2); PL (4); SG (3); IN (7); TU (11); HU (3); US (7); ES (8)