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

Last updated on October 5, 2018

FOR MORE INFORMATION
Study Location
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Leukemia, Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC LEUKEMIA
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-75 years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5%
blasts) and who are eligible for HSCT;

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

1. Isolated extramedullary relapse (ie, testicular or central nervous system);

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.

NCT03677596
Pfizer
Not yet recruiting
A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

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Pfizer Clinical Trials Contact Center

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[email protected]

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A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
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.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

  • Leukemia
  • Precursor b-Cell Lymphoblastic Leukemia-Lymphoma
  • ACUTE LYMPHOBLASTIC LEUKEMIA
  • Drug: 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.
    Other Name: Besponsa
  • Drug: 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 Name: Besponsa
  • Experimental: 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)
    Intervention: Drug: inotuzumab ozogamicin-dose level 2
  • Active Comparator: 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)
    Intervention: Drug: Inotuzumab ozogamicin-dose level 1
Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
102
Same as current
May 2025
May 2024   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (?5% blasts) and who are eligible for HSCT;
  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:

  1. Isolated extramedullary relapse (ie, testicular or central nervous system);
  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.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
No

Contact: Pfizer CT.gov Call Center 1-800-718-1021 [email protected]
Not Provided
 
 
NCT03677596
B1931030
2018-001557-27 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/da...
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
September 2018

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting thte study website. To get updates and notications about this trail, sign up using the form below.

BY PHONE

Pfizer Clinical Trials Contact Center

1-800-718-1021

BY EMAIL

Contact

[email protected]



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