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Study Summary
No. 2012-0151:.......Leukemia......Hagop Kantarjian......Leukemia
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Study Summary Title
Study Summary
Number:
2012-0151
Study Title:An Open-label, Randomized Phase 3 Study of Inotuzumab Ozogamicin Compared to a Defined Investigator's Choice in Adult Patients with Relapsed or Refractory CD22-Positive Acute Lymphoblastic Leukemia (ALL)
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Physician New Patient Referral
Name:Hagop KantarjianPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7026
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Pfizer
Phase of Study:Phase IIIReturn
Visit:
Treatment
Agents:
Cytarabine
Fludarabine
G-CSF
Inotuzumab Ozogamicin
Mitoxantrone
Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to compare inotuzumab ozogamicin to
3 other types of chemotherapy treatments when given to patients with relapsed
or refractory ALL. The safety of inotuzumab ozogamicin will also be studied.

Inotuzumab ozogamicin is designed to attach to a protein that is often found in
leukemia cells. This will allow the drug to go inside the cell and may cause
the cancer cells to die.
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Study Objectives / Outcomes
Primary Objective
To compare the hematological remission, defined as complete response (CR) (both CR and CRi [complete response with incomplete count recovery]), reported by the
external independent endpoint adjudication committee, in patients with relapsed/refractory acute lympoblastic leukemia (ALL) randomized to receive inotuzumab ozogamicin (Arm A) versus patients randomized to receive the active comparator (Arm B).

Secondary Objectives
Safety and efficacy endpoints will be compared between the inotuzumab ozogamicin arm and the active comparator arm and will include:

Key Secondary Objective:
  • To compare the overall survival (OS) of patients with relapsed/refractory ALL.

Other Secondary Objectives:
  • To compare the duration of response (DoR);
  • To compare the progression-free survival (PFS);
  • To compare the time to progression (TTP);
  • To compare the rate of stem-cell transplantation in patients;
  • To characterize the safety and tolerability including the rate of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) following allogeneic stem cell transplant;
  • To assess minimal residual disease levels and cytogenetics in patients achieving a CR/CRi;
  • To determine the population pharmacokinetic parameters of inotuzumab and confirm sources of exposure variability;
  • To compare patient-reported health-related quality of life (HRQOL) and patient reported health status between treatment arms.

Exploratory
  • To determine the relationship of inotuzumab exposure (PK [pharmacokinetic] and/or dose) to efficacy and hematological measures for evaluating dosage recommendations associated with optimal response;
  • To evaluate the relationship of inotuzumab concentration on QTcF;
  • To characterize the effect of inotuzumab ozogamicin exposure on circulating micro RNA.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:09/21/2012
Study Type:Phase Iii
Recruitment Status:Open
Projected Accrual:up to 292
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Relapsed or refractory CD22-positive ALL (ie, >/=20% blasts CD22-positive) due to receive either salvage 1 or salvage 2 therapy and for which either arm of randomized study therapy offers a reasonable treatment option. Ph+ ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor;

2) Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;

3) Bone marrow involvement with >/=5% lymphoblasts;

4) Age 18 years or older;

5) ECOG performance status 0-2;

6) 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. If organ function abnormalities are considered due to tumor, total serum bilirubin must be </=2 x ULN;

7) Serum creatinine </= 1.5 x upper limit of normal (ULN) or any serum creatinine level associated with a measured or calculated creatinine clearance of >/=40 mL/min;

8) Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days 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 patients who are not of childbearing potential (ie, meet at least one of the following criteria): Have undergone hysterectomy or bilateral oophorectomy; or Have medically confirmed ovarian failure; or Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause. Acceptable contraception: oral, injected or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); male-condom or female-condom used WITH a spermicide (ie, foam, gel, film, cream, suppository); Male sterilization.

9) Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study;

10) Patients who are 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 CNS);

2) Burkitt's or mixed lineage leukemia;

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: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine, thioguanine, and tyrosine kinase inhibitors are permitted within 2 weeks of randomization as maintenance or to reduce the peripheral blood blast count. Patients must have recovered from acute non hematologic toxicity (to </= Grade 1) of all previous therapy prior to enrollment;

5) Prior monoclonal antibodies within 6 weeks of randomization;

6) Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy </=4 months before randomization. Patients must have completed immunosuppression therapy for treatment of GvHD prior to enrollment. At randomization, patients must not have >/= Grade 2 acute GvHD, or extensive chronic GvHD;

7) Peripheral absolute lymphoblast count >/=10,000 /muL (treatment with hydroxyurea and/or steroids is permitted within 2 weeks of randomization to reduce the WBC count);

8) Known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease);

9) Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice;

10) Major surgery within </=4 weeks before randomization;

11) Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);

12) 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;

13) Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;

14) Patients with active heart disease (NYHA class >/= 3 as assessed by history and physical examination);

15) QTcF > 470 msec (based on the average of 3 consecutive ECGs);

16) Myocardial infarction </=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 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) History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse;

20) History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS);

21) Administration of live vaccine </=6 weeks before randomization;

22) 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;

23) Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies;

24) Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 90 days after the last dose of investigational product;

25) Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial;

26) Participation in other investigational studies during active treatment phase;

27) Other severe acute or chronic medical or psychiatric condition 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 patient inappropriate for entry into this study.

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Links
Registration Number: NCT01564784
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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