Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-positive PC Positive ALL and CML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02311998
Recruitment Status : Recruiting
First Posted : December 9, 2014
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase I/II trial studies the side effects and best dose of bosutinib when given together with inotuzumab ozogamicin and to see how well it works in treating patients with acute lymphoblastic leukemia or chronic myeloid leukemia that has come back or does not respond to treatment. Bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotoxins, such as inotuzumab ozogamicin, are antibodies linked to a toxic substance and may help find cancer cells that express CD22 and kill them without harming normal cells. Giving bosutinib together with inotuzumab ozogamicin may be a better treatment for acute lymphoblastic leukemia or chronic myeloid leukemia.

Condition or disease Intervention/treatment Phase
B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Blasts More Than 5 Percent of Bone Marrow Nucleated Cells CD22 Positive Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive Drug: Bosutinib Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerated dose (MTD) of bosutinib in combination with inotuzumab ozogamicin in patients with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) in lymphoid blast phase that express CD22. (Phase I) II. To determine the efficacy of bosutinib in combination with inotuzumab ozogamicin in patients with Ph+ ALL and CML in lymphoid blast phase that express CD22. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the efficacy of bosutinib in combination with inotuzumab ozogamicin in patients with Ph+ ALL and CML in lymphoid blast phase that express CD22. (Phase I) II. To determine the duration of response of patients treated with this combination. (Phase I) III. To determine the overall survival of patients treated with this combination. (Phase I) IV. To determine the effect of the level of pre-treatment expression of CD22 with response to this combination. (Phase I) V. To determine the efficacy of this combination according to pre-treatment mutation status in the ABL kinase domain. (Phase I) VI. To determine the minimal residual disease after treatment with this combination and its impact in long-term outcome. (Phase I) VII. To determine the safety bosutinib in combination with inotuzumab ozogamicin in patients with Ph+ ALL and CML in lymphoid blast phase that express CD22. (Phase II) VIII. To determine the duration of response of patients treated with this combination. (Phase II) IX. To determine the overall survival of patients treated with this combination. (Phase II) X. To determine the effect of the level of pre-treatment expression of CD22 with response to this combination. (Phase II) XI. To determine the efficacy of this combination according to pre-treatment mutation status in the abl kinase domain. (Phase II) XII. To determine the minimal residual disease after treatment with this combination and its impact in long-term outcome. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of bosutinib followed by a phase II study.

Patients receive bosutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 1, 8, and 15. Patients with confirmed complete response (CR), incomplete blood count recovery (CRi), complete cytogenetic response (CCyR) and/or absence of minimal residual disease (MRD) may receive inotuzumab ozogamicin IV on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 1 year.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-Positive Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia Lymphoid Blast Phase
Actual Study Start Date : April 16, 2015
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020


Arm Intervention/treatment
Experimental: Treatment (bosutinib, inotuzumab ozogamicin)
Patients receive bosutinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Patients with confirmed CR, CRi, CCyR and/or absence of MRD may receive inotuzumab ozogamicin IV on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Bosutinib
Given PO
Other Names:
  • Bosulif
  • SKI 606
  • SKI-606

Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Maximum tolerated dose of bosutinib defined as the highest dose level in which < 2 patients of 6 develop first course dose limiting toxicity (Phase I) [ Time Frame: At day 28 ]
    Will be observed.

  2. Major hematologic response for relapsed Philadelphia positive acute lymphoblastic leukemia (MaHR) (Phase II) [ Time Frame: Up to 16 weeks (cycle 4 of treatment) ]
    The response will be evaluated along with its 95% confidence interval.

  3. Complete response/complete response with incomplete bone marrow recovery for newly diagnosed Philadelphia positive acute lymphoblastic leukemia or chronic myeloid leukemia or chronic myeloid leukemia- lymphoid blast phase with age >= 60 (Phase II) [ Time Frame: Up to 1 year after completion of study treatment ]
    Will be observed.


Secondary Outcome Measures :
  1. Overall major hematologic response (Phase I) [ Time Frame: Up to 1 year after completion of study treatment ]
    Will be observed.

  2. Duration of response (Phase I) [ Time Frame: Up to 1 year after completion of study treatment ]
    Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events and the potential prognostic factors.

  3. Overall survival (OS) (Phase I) [ Time Frame: Up to 1 year after completion of study treatment ]
    Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.

  4. Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase II) [ Time Frame: Up to 1 year after completion of study treatment ]
    Safety data will be summarized by category, severity and frequency.

  5. Duration of response (Phase II) [ Time Frame: Up to 1 year after completion of study treatment ]
    Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events and the potential prognostic factors.

  6. Overall survival (Phase II) [ Time Frame: Up to 1 year after completion of study treatment ]
    Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening
  • Expression of CD-22 in >= 20% blasts
  • Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2
  • Serum bilirubin < or = 2.0 mg/dl
  • Serum creatinine < or = 2.0 mg/dl
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN)
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
  • Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
  • Patients or their legally authorized representative must provide written informed consent

Exclusion Criteria:

  • History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
  • Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded
  • Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration
  • Previous treatment with any anti-CD22 directed therapy
  • Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria:

    • < 100 days from allogeneic SCT
    • Active acute or chronic graft-versus-host disease (GvHD), or
    • Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days
  • Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible
  • Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
  • Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse
  • History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable
  • Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions:

    • To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents
    • For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI)
  • Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment
  • Females who are pregnant or lactating
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
  • Patients previously exposed to bosutinib are eligible unless they carry T315I
  • Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02311998


Contacts
Layout table for location contacts
Contact: Nitin Jain, MBBS 713-792-7305

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Nitin Jain    713-792-7305      
Principal Investigator: Nitin Jain         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Nitin Jain M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02311998     History of Changes
Other Study ID Numbers: 2014-0435
NCI-2014-02606 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0435 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: December 9, 2014    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Inotuzumab Ozogamicin
Antineoplastic Agents