Clinical Trials /

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

NCT01371630

Description:

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 asnotuzumab 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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Acute Lymphoblastic Leukemia
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 2010-0991
  • SECONDARY ID: NCI-2011-01123
  • SECONDARY ID: 2010-0991
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01371630

Conditions

  • Acute Lymphoblastic Leukemia
  • B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
  • Untreated Adult Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Treatment (inotuzumab ozogamicin, combination chemotherapy)
Cyclophosphamide(-)-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- 138719Treatment (inotuzumab ozogamicin, combination chemotherapy)
Cytarabine.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-28453Treatment (inotuzumab ozogamicin, combination chemotherapy)
Inotuzumab OzogamicinBesponsa, CMC-544, Way 207294, WAY-207294Treatment (inotuzumab ozogamicin, combination chemotherapy)
Mercaptopurine3H-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-2785Treatment (inotuzumab ozogamicin, combination chemotherapy)
MethotrexateAbitrexate, 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-19039Treatment (inotuzumab ozogamicin, combination chemotherapy)
Prednisone.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, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-PrednisoneTreatment (inotuzumab ozogamicin, combination chemotherapy)
RituximabABP 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, RTXM83Treatment (inotuzumab ozogamicin, combination chemotherapy)
Vincristine SulfateKyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateTreatment (inotuzumab ozogamicin, combination chemotherapy)

Purpose

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 asnotuzumab 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.

Detailed Description

      PRIMARY OBJECTIVES:

      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)

      EXPLORATORY OBJECTIVES:

      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.

      COURSES 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 course 1 and
      day 2 or 3 of course 3; methotrexate intrathecally (IT) on day 2 of courses 1 and 3; and
      cytarabine IT on day 8 of courses 1 and 3. Patients may also receive rituximab IV on days 1
      and 8 of courses 1 and 3. Courses alternate every 3-4 weeks in the absence of disease
      progression or unacceptable toxicity.

      COURSES 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 courses
      2 and 4; cytarabine IT on day 5 of courses 2 and 4; and methotrexate IT on day 8 of courses 2
      and 4. Patients may also receive rituximab IV on days 1 and 8 of courses 2 and 4. Courses
      alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

      COURSES 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 courses 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 courses of blinatumomab as in
      courses 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 courses
      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (inotuzumab ozogamicin, combination chemotherapy)ExperimentalSee Detailed Description
  • Blinatumomab
  • Cyclophosphamide
  • Cytarabine
  • Inotuzumab Ozogamicin
  • Mercaptopurine
  • Methotrexate
  • Prednisone
  • Rituximab
  • Vincristine Sulfate

Eligibility Criteria

        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, provided they are not
             eligible for regimens of higher priority

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities, defined as non-hematologic grade 3 or 4 toxicities during the first course (Phase I)
Time Frame:28 days
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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