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

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. Identifier: NCT01371630
Recruitment Status : Recruiting
First Posted : June 13, 2011
Last Update Posted : October 25, 2019
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 inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating older patients with previously untreated acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and 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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative Untreated Adult Acute Lymphoblastic Leukemia Biological: Blinatumomab Drug: Cyclophosphamide Drug: Cytarabine Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Drug: Mercaptopurine Drug: Methotrexate Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate Phase 1 Phase 2

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Detailed Description:


I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic leukemia (ALL). (Phase I) II. Evaluate the efficacy of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients with ALL. (Phase II) III. To evaluate the side effects of the treatment. (Phase II) IV. Evaluate the regimen efficacy in refractory-relapsed ALL. (Phase II)


I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVD (cyclophosphamide, dexamethasone, methotrexate, and cytarabine) + inotuzumab + blinatumomab.

II. To evaluate the impact of next generation sequencing (NGS)-based minimal residual disease (MRD) assay on outcomes and to compare with standard flow cytometry MRD assays.

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

CYCLES 1, 3, 7, AND 9: Patients receive cyclophosphamide intravenously (IV) over approximately 3 hours twice daily (BID) on days 1-3; vincristine sulfate IV over 30 minutes on days 1 and 8; inotuzumab ozogamicin IV over approximately 1 hour on day 3 of cycle 1 and day 2 or 3 of cycle 3; methotrexate intrathecally (IT) on day 2 of cycles 1 and 3; and cytarabine IT on day 8 of cycles 1 and 3. Patients may also receive rituximab IV on days 1 and 8 of cycles 1 and 3. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

CYCLES 2, 4, 8, AND 10: Patients receive methotrexate IV over approximately 2 hours and then continuously over approximately 22 hours on day 1; cytarabine IV over approximately 3 hours BID on days 2-3; inotuzumab ozogamicin IV over approximately 1 hour on day 2 or 3 of cycles 2 and 4; cytarabine IT on day 5 of cycles 2 and 4; and methotrexate IT on day 8 of cycles 2 and 4. Patients may also receive rituximab IV on days 1 and 8 of cycles 2 and 4. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

CYCLES 5, 6, 11, AND 12: Patients receive blinatumomab as a continuous intravenous infusion (CIVI) on days 1-29. Treatment repeats every 42 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive mercaptopurine orally (PO) BID and methotrexate PO once weekly for 3 years. Patients also receive vincristine sulfate IV over 30 minutes once monthly and prednisone PO daily five times a month for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who did not receive blinatumomab during induction and consolidation can receive 4 consecutive cycles of blinatumomab as in cycles 5, 6, 11, and 12, at any time during maintenance, after discussion with the principal investigator and if in the best interest of the patient.

TREATMENT OF MINIMAL RESIDUAL DISEASE (MRD): Patients with MRD may receive additional cycles of inotuzumab ozogamicin IV every 3-4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 4 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 256 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-Intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)
Actual Study Start Date : August 26, 2011
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Arm Intervention/treatment
Experimental: Treatment (inotuzumab ozogamicin, combination chemotherapy)
See Detailed Description
Biological: Blinatumomab
Given CIVI
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • Blincyto
  • MEDI-538
  • MT-103

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Cytarabine
Given IT and IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

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

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Mercaptopurine
Given PO
Other Names:
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • BW 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785

Drug: Methotrexate
Given IT, IV, and PO
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Drug: Prednisone
Given PO
Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • rituximab biosimilar TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

Primary Outcome Measures :
  1. Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I) [ Time Frame: 28 days ]
    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.

  2. Progression free survival (PFS) in frontline elderly acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: 2 years ]
    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.

  3. Response rate in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: Up to 5 years ]
    The precise complete remission (CR) and marrow CR rate will be defined.

  4. Survival in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II) [ Time Frame: Up to 1 year ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with previously untreated ALL of pre-B, Philadelphia chromosome (Ph-) negative ALL; minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed
  • Zubrod performance status 0-3
  • Bilirubin =< 1.95 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) =< 3 x upper limit of normal (ULN) unless considered due to tumor
  • Creatinine =< 2 mg/dL
  • 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
  • Patients in first remission are eligible
  • Patients with refractory-relapsed ALL of any age are eligible

Exclusion Criteria:

  • Ph-positive ALL, Burkitt's leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma
  • Patient with active heart disease (New York Heart Association [NYHA] class >= 3 as assessed by history and physical examination)
  • Patients with a cardiac ejection fraction (as measured by either multigated acquisition scan [MUGA] or echocardiogram) < 40% are excluded
  • Patients with active hepatitis are excluded
  • Pregnant or breast-feeding women are excluded

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 identifier (NCT number): NCT01371630

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Contact: Elias Jabbour 713-792-7026

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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Elias Jabbour    713-792-7026      
Principal Investigator: Elias Jabbour         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Elias Jabbour M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01371630     History of Changes
Other Study ID Numbers: 2010-0991
NCI-2011-01123 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2010-0991 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: June 13, 2011    Key Record Dates
Last Update Posted: October 25, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Inotuzumab Ozogamicin
Antineoplastic Agents, Immunological
Antibodies, Monoclonal
Antibodies, Bispecific