• Complete response (CR) rate [ Time Frame: Up to 5 years ]
  Rate of complete response (CR) by bone marrow morphology and/or imaging.
• Rate of complete minimal residual disease (MRD) response [ Time Frame: Up to 5 years ]
  Assessed by multiparameter flow cytometry (MFC).
• Progression-free survival [ Time Frame: Up to 5 years ]
• Relapse-free survival [ Time Frame: Up to 5 years ]
• Overall survival [ Time Frame: Up to 5 years ]
• Rate at which patients proceed to subsequent allogeneic hematopoietic cell transplantation (HCT) [ Time Frame: Up to 5 years ]

This is a dose-escalation study of inotuzumab ozogamicin.

Patients receive etoposide, doxorubicin, and vincristine intravenously (IV) via continuous infusion on days 1-4, prednisone orally (PO) or IV twice daily (BID) on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 8 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days then annually for up to 5 years.

• Recurrent B Acute Lymphoblastic Leukemia
• Recurrent B Lymphoblastic Lymphoma
• Refractory B Acute Lymphoblastic Leukemia
• Refractory B Lymphoblastic Lymphoma

• Drug: Etoposide
  Given IV
  Other Names:

  • 33419-42-0
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16
  • 141540
• Drug: Doxorubicin
  Given IV
  Other Names:

  • 14-Hydroxydaunomycin
  • 23214-92-8
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin
• Drug: Vincristine
  Given IV
  Other Names:

  • 22-Oxovincaleukoblastine
  • LEUROCRISTINE
  • VCR
  • Vincrystine
• Drug: Prednisone
  Given PO or IV
  Other Names:

  • 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Metacortandracin
  • Ofisolona
  • Orasone
  • Paracort
  • Predicor
  • Predicorten
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
• Drug: Cyclophosphamide
  Given IV
  Other Names:

  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclostin
  • Cyclostine
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
• Biological: Inotuzumab Ozogamicin
  Given IV
  Other Names:

  • 635715-01-4
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

• Experimental: Dose -1 (0.3 mg/m^2)
  Patients receive etoposide, doxorubicin, and vincristine IV via continuous infusion on days 1-4, prednisone PO or IV BID on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Patients also receive inotuzumab ozogamicin IV over 1 hour on day 8. Treatment repeats approximately every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Etoposide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Cyclophosphamide
  • Biological: Inotuzumab Ozogamicin
• Experimental: Dose 1 (0.3 mg/m^2)
  Dose 1 patients receive etoposide, doxorubicin, and vincristine IV via continuous infusion on days 1-4, prednisone PO or IV BID on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 8 and 15. Treatment repeats approximately every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Etoposide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Cyclophosphamide
  • Biological: Inotuzumab Ozogamicin
• Experimental: Dose 2 (0.6 mg/m^2, 0.3 mg/m^2)
  Dose 2 patients receive etoposide, doxorubicin, and vincristine IV via continuous infusion on days 1-4, prednisone PO or IV BID on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 8 and 15. Treatment repeats approximately every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Etoposide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Cyclophosphamide
  • Biological: Inotuzumab Ozogamicin
• Experimental: Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)
  Dose 3 patients receive etoposide, doxorubicin, and vincristine IV via continuous infusion on days 1-4, prednisone PO or IV BID on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 8 and 15. Treatment repeats approximately every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Etoposide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Cyclophosphamide
  • Biological: Inotuzumab Ozogamicin

Inclusion Criteria:

• Patients must have a confirmed diagnosis of CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. CD22 expression will be determined by multiparameter flow cytometry (MFC) or immunohistochemistry.

• Relapsed or refractory disease, as defined by any of the following:

  • Unable to achieve complete response (CR) despite >= 4 weeks of initial course of systemic therapy.

  • Recurrence of disease at any point after CR was achieved.

    • (Note: patients with Ph-positive disease must have received >= 1 second- or third-generation ABL kinase inhibitor as part of their prior treatment to be eligible.)

• Detectable disease, as defined by any of the following:

  • Presence of >= 5% abnormal blasts in the bone marrow or peripheral blood by morphology or MFC.
  • Patients with isolated extramedullary disease will be permitted if there is >= 1 site of disease that measures >= 1.5 cm in longest diameter on cross-sectional imaging.
• Absolute neutrophil count (ANC) >= 1,000/uL.
• Hemoglobin >= 8 g/dL.
• Platelets >= 50,000/uL.
• Note: Transfusions and growth factor support will be permitted within 3 days of initiation of study treatment to reach these thresholds. As patients with relapsed/refractory ALL frequently have cytopenias due to marrow infiltration by the disease, no hematologic parameters will be required for enrollment if cytopenias can be attributed to disease.
• Total serum bilirubin =< 1.5 x upper limit of normal (ULN); (unless due to Gilbert syndrome or hemolysis; =< 2 x ULN for hepatic abnormalities considered disease-related).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN.
• Serum creatinine =< 1.5 x ULN or serum creatinine level associated with a measured or calculated creatinine clearance of >= 40 mL/min.
• Corrected QT (QTc) interval =< 500 msec; if assessed, left ventricular ejection fraction >= 40%.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Must agree to the use of effective contraception while on study treatment, unless they are highly unlikely to conceive (defined as [1] surgically sterilized, or [2] women who are and men whose sexual partner[s] is/are postmenopausal [i.e., a woman who is > 50 years old or who has not had menses for >= 1 year], or [3] not heterosexually active for the duration of the study).

Exclusion Criteria:

• Patients with a circulating blast count of > 50,000/uL; systemic therapy with either hydroxyurea, vincristine, and/or corticosteroids will be permitted within 3 days of initiation of study treatment to reduce the blast count.

• Except for management of circulating blasts noted above, adequate duration from prior therapy must be achieved before initiation of study treatment, as defined below:

  • No cytotoxic or targeted systemic therapy < 2 weeks or 5 half-lives (whichever is shorter).
  • No blinatumomab < 2 weeks.
  • No radiation therapy < 4 weeks.
  • No monoclonal antibody therapy < 6 weeks (except for prior InO, as discussed below).

• Patients previously treated with InO will be eligible, unless they meet ANY of the following criteria:

  • > 6 individual doses (e.g., > 2 standard cycles) were administered.
  • Any documented hepatic toxicity observed was grade 3 or higher.
  • The most recent dose was administered < 3 months from the initiation of study treatment.
• For patients that have received prior allogeneic HCT, they must be >= 4 months from the date of stem cell infusion, with no prior history of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), and off all treatment for graft-vs-host disease (GVHD) for >= 2 weeks. Patients with minimal active symptoms that can be controlled with topical therapies and/or the equivalent of prednisone =< 10 mg/day will be eligible.
• For patients that have received other forms of cellular immunotherapy (e.g., chimeric antigen receptor-modified [CAR] T cells), they must be >= 21 days from cell infusion, and any specific manifestations of cytokine release syndrome or neurologic toxicity attributable to the cellular therapy have completely resolved (i.e., < grade 1)
• Patients with a known history of chronic liver disease, including but not limited to cirrhosis, steatohepatitis, and chronic viral hepatitis. Patients with a history of GVHD of the liver will be permitted, provided they meet all of the other eligibility criteria.
• Patients with isolated testicular or central nervous system disease.
• Known hypersensitivity or intolerance to any of the agents under investigation.
• May not be pregnant or nursing.

• National Cancer Institute (NCI)
• Pfizer