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

NCT03991884 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: RG1004854NCI-2019-038118786
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of inotuzumab ozogamicin (InO)

  Will be defined as the highest dose of InO administered in which the incidence of dose limiting toxicities (DLTs) is \< 33%, assuming at least 6 patients have been treated at this dose. DLTs assessed by: * Non-hematologic toxicities \>= grade 3 evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 (except for febrile neutropenia/infection, unless felt to be a direct consequence of treatment-related toxicity \[e.g., intestinal infection following mucosal barrier breakdown\]). * Any instance of possible, probably, or definite SOS/VOD * Inability to complete 1 full cycle due to treatment-related adverse events * Any treatment delays \> 3 weeks (i.e., to Day 50 of Cycle 1) for recovery of prolonged toxicity

  Up to 5 years

Secondary Outcomes (6)

• Complete response (CR) rate

  Up to 5 years

• Rate of complete minimal residual disease (MRD) response

  Up to 5 years

• Progression-free survival

  Up to 5 years

• Relapse-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (4)

Dose -1 (0.3 mg/m^2)

EXPERIMENTAL

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.

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

Dose 1 (0.3 mg/m^2)

EXPERIMENTAL

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.

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

Dose 2 (0.6 mg/m^2, 0.3 mg/m^2)

EXPERIMENTAL

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.

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

Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

EXPERIMENTAL

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.

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

Interventions

Etoposide DRUG

Given IV

Also known as: 33419-42-0, Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16, 141540

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Doxorubicin DRUG

Given IV

Also known as: 14-Hydroxydaunomycin, 23214-92-8, Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Vincristine DRUG

Given IV

Also known as: 22-Oxovincaleukoblastine, LEUROCRISTINE, VCR, Vincrystine

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Prednisone DRUG

Given PO or IV

Also known as: 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

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Cyclophosphamide DRUG

Given IV

Also known as: 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

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Inotuzumab Ozogamicin BIOLOGICAL

Given IV

Also known as: 635715-01-4, Besponsa, CMC-544, Way 207294, WAY-207294

Dose -1 (0.3 mg/m^2); Dose 1 (0.3 mg/m^2); Dose 2 (0.6 mg/m^2, 0.3 mg/m^2); Dose 3 (0.6 mg/m^2, 0.3 mg/m^2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead
• Pfizer: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 38722664 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Etoposide; Doxorubicin; Vincristine; Prednisone; Cyclophosphamide; Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ryan Cassaday

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 19, 2019
• Study Start: September 24, 2019
• Primary Completion: October 20, 2022
• Study Completion: June 28, 2023
• Last Updated: July 6, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)