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

NCT02311998 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2014-0435NCI-2014-02606
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Bosutinib All Phase I Participants

  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). Dose levels assessed were dose 1 = 300 mg, dose 2 = 400 mg, and dose 3 = 500 mg.

  At day 28

• Number of Participants With a Major Hematologic Response

  Major Hematologic Response i(MaHR) is defined as Complete Response (CR) + Complete Remission without Incomplete Blood Count Recovery (CRi). CR was defined as absence of circulating blasts with bone marrow blasts \<5% and recovery of neutrophil count to ≥1.0 x 10\^9/L and platelet count to ≥100 x10\^9/L. The CRi was defined as meeting criteria for CR except for neutrophil and/or platelet recovery. Response was assessed by bone marrow analysis after each cycle of therapy until attainment of CR/CRi.

  Up to 6 years, 11 months

Secondary Outcomes (2)

• Duration of Response

  Up to 6 years, 11 months

• Overall Survival (OS)

  Up to 6 years, 11 months

Study Arms (4)

Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 1

EXPERIMENTAL

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; Biological: Inotuzumab Ozogamicin

Treatment (bosutinib, inotuzumab ozogamicin) Phase II

EXPERIMENTAL

Patients receive bosutinib at the Maximum Tolerated Dose from the Phase I dose part, 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; Biological: Inotuzumab Ozogamicin

Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 2

EXPERIMENTAL

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; Biological: Inotuzumab Ozogamicin

Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 3

EXPERIMENTAL

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; Biological: Inotuzumab Ozogamicin

Interventions

Bosutinib DRUG

Given PO

Also known as: Bosulif, SKI 606, SKI-606

Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 1; Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 2; Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 3; Treatment (bosutinib, inotuzumab ozogamicin) Phase II

Inotuzumab Ozogamicin BIOLOGICAL

Given IV

Also known as: Besponsa, CMC-544, Way 207294, WAY-207294

Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 1; Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 2; Treatment (bosutinib, inotuzumab ozogamicin) Phase I Dose 3; Treatment (bosutinib, inotuzumab ozogamicin) Phase II

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

bosutinib; Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: Nitin Jain MD/Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

njain@mdanderson.org

713-745-6080

Study Officials

• Nitin Jain

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 9, 2014
• Study Start: April 16, 2015
• Primary Completion: March 23, 2022
• Study Completion: March 23, 2022
• Last Updated: July 17, 2023
• Results First Posted: July 17, 2023

Record last verified: 2023-07

Locations

US (1)