Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia

NCT01371630 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2010-0991NCI-2011-01123
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating patients with acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH). Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin together with combination chemotherapy may be a better treatment for acute lymphoblastic leukemia.

Conditions

B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Burkitt-Like Lymphoma With 11q Aberration; High Grade B-Cell Lymphoma, Not Otherwise Specified; High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Burkitt Lymphoma; Refractory B Acute Lymphoblastic Leukemia; Refractory Burkitt Lymphoma

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I)

  Defined as non-hematologic grade 3 or 4 toxicities during the first course. Toxicities will be monitored using the method of Thall, Simon, and Estey. Adverse events will be summarized and toxicity rate will be estimated with a 90% credible interval.

  28 days

• Progression free survival (PFS) in frontline elderly acute lymphoblastic leukemia (ALL) (Phase II)

  Bayesian time-to-event model will be used. Kaplan and Meier product limit method will be used to estimate the PFS along with the 95% confidence intervals for the median PFS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.

  2 years

• Response rate in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)

  The precise complete remission (CR) and marrow CR rate will be defined.

  Up to 5 years

• Survival in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)

  The median and 1-year survival rate will be defined. Kaplan and Meier product limit method will be used to estimate the overall survival (OS) along with the 95% confidence intervals for the median OS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.

  Up to 1 year

Study Arms (3)

Arm I (inotuzumab ozogamicin, combination chemotherapy)

EXPERIMENTAL

See Detailed Description Arm I

Biological: Blinatumomab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Biological: Inotuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine

Arm II (inotuzumab ozogamicin, combination chemotherapy)

EXPERIMENTAL

See Detailed Description Arm II

Biological: Blinatumomab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Biological: Inotuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine

Arm III (inotuzumab ozogamicin, combination chemotherapy)

EXPERIMENTAL

See Detailed Description Arm III

Biological: Blinatumomab; Drug: Cytarabine; Drug: Dexamethasone; Biological: Inotuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Biological: Rituximab; Drug: Vincristine

Interventions

Mercaptopurine DRUG

Given PO

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy)

Methotrexate DRUG

Given IT, IV, and PO

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Prednisone DRUG

Given PO

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy)

Rituximab BIOLOGICAL

Given IV

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Vincristine DRUG

Given IV

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Blinatumomab BIOLOGICAL

Given CIVI

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Cyclophosphamide DRUG

Given IV

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy)

Cytarabine DRUG

Given IT and IV

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Dexamethasone DRUG

Given IV or PO

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Inotuzumab Ozogamicin BIOLOGICAL

Given IV

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (inotuzumab ozogamicin, combination chemotherapy); Arm II (inotuzumab ozogamicin, combination chemotherapy); Arm III (inotuzumab ozogamicin, combination chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Patients age 60 years or older with previously untreated ALL pre-B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL Minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed.
• Patients unfit ≥ 18 - \< 60 years of age with previously untreated ALL pre- B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL (includes patients initiated on first cycle of hyper-CVAD before cytogenetics known. These patients could have received one or two cycles of chemotherapy with or without other TKIs and still eligible.
• These patients are defined as having at least one of the below comorbidities:
• ECOG performance status ≥ 2
• Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Severe pulmonary disorder (e.g., DLCO ≤ 65% or FEV1 ≤ 65%)
• Creatinine clearance \< 45 mL/min, and
• Hepatic disorder with total bilirubin \> 1.5 x upper limit of normal
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• If they achieved CR, they are assessable only for event-free and overall survival, or
• If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
• Patients age 60 years and older unfit for intensive chemotherapy with one or more comorbidities (e.g., renal insufficiency, heart disease, cardio-vascular disease, uncontrolled hypertension, diabetes, respiratory problems, among others) and a PS of ≥ 1. All ages of Jehovah's witness are eligible.
• Zubrod performance status 0-3.
• Adequate liver function (bilirubin \< 1.95 mg/dL and SGPT or SGOT \< 3 x upper limit of normal \[ULN\], unless considered due to tumor), and renal function (estimated creatinine clearance ≥50 mL/min/1.73 m2). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is \< 2.6 mg/dL and creatinine \< 3 mg/dL.
• Provision of written informed consent.

You may not qualify if:

• Newly diagnosed Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic lymphoma.
• Patient with active heart disease (NYHA class \> 3 as assessed by history and physical examination).
• Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) \< 40% are excluded.
• Patients with active hepatitis are excluded.
• Pregnant or breast-feeding women are excluded.

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

RECRUITING

Related Publications (6)

• Zhao Y, Short NJ, Kantarjian HM, Chang TC, Ghate PS, Qu C, Macaron W, Jain N, Thakral B, Phillips AH, Khoury J, Garcia-Manero G, Zhang W, Fan Y, Yang H, Garris RS, Nasr LF, Kriwacki RW, Roberts KG, Konopleva M, Jabbour EJ, Mullighan CG. Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. Blood. 2024 Jul 4;144(1):61-73. doi: 10.1182/blood.2024023930.

  PMID: 38551807 DERIVED

• Jabbour E, Short NJ, Senapati J, Jain N, Huang X, Daver N, DiNardo CD, Pemmaraju N, Wierda W, Garcia-Manero G, Montalban Bravo G, Sasaki K, Kadia TM, Khoury J, Wang SA, Haddad FG, Jacob J, Garris R, Ravandi F, Kantarjian HM. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial. Lancet Haematol. 2023 Jun;10(6):e433-e444. doi: 10.1016/S2352-3026(23)00073-X. Epub 2023 May 12.

  PMID: 37187201 DERIVED

• Kantarjian H, Haddad FG, Jain N, Sasaki K, Short NJ, Loghavi S, Kanagal-Shamanna R, Jorgensen J, Khouri I, Kebriaei P, Alvarado Y, Kadia T, Paul S, Garcia-Manero G, Dabaja B, Yilmaz M, Jacob J, Garris R, O'Brien S, Ravandi F, Jabbour E. Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. J Hematol Oncol. 2023 May 2;16(1):44. doi: 10.1186/s13045-023-01444-2.

  PMID: 37131217 DERIVED

• 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

• Kantarjian H, Ravandi F, Short NJ, Huang X, Jain N, Sasaki K, Daver N, Pemmaraju N, Khoury JD, Jorgensen J, Alvarado Y, Konopleva M, Garcia-Manero G, Kadia T, Yilmaz M, Bortakhur G, Burger J, Kornblau S, Wierda W, DiNardo C, Ferrajoli A, Jacob J, Garris R, O'Brien S, Jabbour E. Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2018 Feb;19(2):240-248. doi: 10.1016/S1470-2045(18)30011-1. Epub 2018 Jan 16.

  PMID: 29352703 DERIVED

• Jabbour E, Ravandi F, Kebriaei P, Huang X, Short NJ, Thomas D, Sasaki K, Rytting M, Jain N, Konopleva M, Garcia-Manero G, Champlin R, Marin D, Kadia T, Cortes J, Estrov Z, Takahashi K, Patel Y, Khouri MR, Jacob J, Garris R, O'Brien S, Kantarjian H. Salvage Chemoimmunotherapy With Inotuzumab Ozogamicin Combined With Mini-Hyper-CVD for Patients With Relapsed or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Feb 1;4(2):230-234. doi: 10.1001/jamaoncol.2017.2380.

  PMID: 28859185 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

blinatumomab; Cyclophosphamide; Cytarabine; Dexamethasone; Inotuzumab Ozogamicin; Mercaptopurine; Methotrexate; Prednisone; Rituximab; Vincristine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Pregnadienediols; Antibodies, Monoclonal, Murine-Derived; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Elias Jabbour, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elias Jabbour, MD

CONTACT

713-792-7026; ejabbour@mdanderson.org

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: June 9, 2011
• First Posted: June 13, 2011
• Study Start: August 26, 2011
• Primary Completion (Estimated): December 25, 2027
• Study Completion (Estimated): December 25, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (1)