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

NCT03991884

Last updated date
Study Location
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Contact
206-606-1202

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.


- 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.

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Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic LymphomaInotuzumab Ozogamicin and Chemotherapy in Treating Patients With Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
NCT03991884
  1. Seattle, Washington
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
Official Title  ICMJE A Phase I Study of Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin Plus Escalating Doses of Inotuzumab Ozogamicin (DA-EPOCH-InO) in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent B Acute Lymphoblastic Leukemia
  • Recurrent B Lymphoblastic Lymphoma
  • Refractory B Acute Lymphoblastic Leukemia
  • Refractory B Lymphoblastic Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2026
Estimated Primary Completion Date February 28, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ryan Cassaday206-606-1202[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03991884
Other Study ID Numbers  ICMJE RG1004854
NCI-2019-03811 ( Registry Identifier: NCI / CTRP )
8786 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Pfizer
Investigators  ICMJE
Principal Investigator:Ryan CassadayFred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP