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

NCT ID: NCT03991884

Last Updated: 2023-07-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-24

Study Completion Date

2023-06-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Etoposide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO or IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Etoposide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO or IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Etoposide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO or IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Etoposide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO or IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type BIOLOGICAL

Given IV

Interventions

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Etoposide

Given IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Vincristine

Given IV

Intervention Type DRUG

Prednisone

Given PO or IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Inotuzumab Ozogamicin

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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33419-42-0 Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 141540 14-Hydroxydaunomycin 23214-92-8 Adriablastin Hydroxydaunomycin Hydroxyl Daunorubicin Hydroxyldaunorubicin 22-Oxovincaleukoblastine LEUROCRISTINE VCR Vincrystine 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 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 635715-01-4 Besponsa CMC-544 Way 207294 WAY-207294

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ryan Cassaday

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Kopmar NE, Quach K, Gooley TA, Martino CH, Cherian S, Percival MM, Halpern AB, Ghiuzeli CM, Oehler VG, Abkowitz JL, Walter RB, Cassaday RD. Dose-Adjusted EPOCH Plus Inotuzumab Ozogamicin in Adults With Relapsed or Refractory B-Cell ALL: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2024 Jul 1;10(7):961-965. doi: 10.1001/jamaoncol.2024.0967.

Reference Type DERIVED
PMID: 38722664 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2019-03811

Identifier Type: REGISTRY

Identifier Source: secondary_id

8786

Identifier Type: OTHER

Identifier Source: secondary_id

RG1004854

Identifier Type: -

Identifier Source: org_study_id

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