Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia

  • STATUS
    Recruiting
  • End date
    Feb 28, 2026
  • participants needed
    24
  • sponsor
    University of Washington
Updated on 5 June 2022

Summary

This phase I trial studies the best dose of inotuzumab ozogamicin in combination with chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has come back (recurrent) or that does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, 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 in combination with chemotherapy may kill more cancer cells than with chemotherapy alone in treating patients with recurrent or refractory B-cell acute lymphoblastic leukemia.

Description

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.

Details
Condition Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
Treatment cyclophosphamide, doxorubicin hydrochloride, etoposide, prednisone, vincristine sulfate, vincristine, doxorubicin, Inotuzumab Ozogamicin
Clinical Study IdentifierNCT03991884
SponsorUniversity of Washington
Last Modified on5 June 2022

Eligibility

Yes No Not Sure

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
> 6 individual doses (e.g., > 2 standard cycles) were administered
following criteria
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 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)
For patients that have received prior allogeneic HCT, they must be >= 4 months from
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
the date of stem cell infusion, with no prior history of sinusoidal
Patients with isolated testicular or central nervous system disease
obstruction syndrome/veno-occlusive disease (SOS/VOD), and off all treatment
for graft-vs-host disease (GVHD) for >= 2 weeks. Patients with minimal active
Known hypersensitivity or intolerance to any of the agents under investigation
May not be pregnant or nursing
symptoms that can be controlled with topical therapies and/or the equivalent
of prednisone =< 10 mg/day will be eligible
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