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Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia

ConditionsB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1B Acute Lymphoblastic Leukemia, Philadelphia Chromosome NegativeBurkitt-Like Lymphoma With 11q AberrationHigh Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsHigh Grade B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent B Acute Lymphoblastic LeukemiaRecurrent Burkitt LymphomaRefractory B Acute Lymphoblastic LeukemiaRefractory Burkitt Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorM.D. Anderson Cancer Center

About this trial

This phase I/II trial studies the side effects and best dose of inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating patients with acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH). Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy 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 together with combination chemotherapy may be a better treatment for acute lymphoblastic leukemia.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients age 60 years or older with previously untreated ALL pre-B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL Minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed.

Patients unfit ≥ 18 - < 60 years of age with previously untreated ALL pre- B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL (includes patients initiated on first cycle of hyper-CVAD before cytogenetics known. These patients could have received one or two cycles of chemotherapy with or without other TKIs and still eligible.

ECOG performance status ≥ 2

Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)

Disqualifiers

Newly diagnosed Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic lymphoma.

Patient with active heart disease (NYHA class > 3 as assessed by history and physical examination).

Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) < 40% are excluded.

Patients with active hepatitis are excluded.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Blinatumomab

    Biological/Vaccine

    Given CIVI

  • Cyclophosphamide

    Drug

    Given IV

  • Cytarabine

    Drug

    Given IT and IV

  • Dexamethasone

    Drug

    Given IV or PO

  • Inotuzumab Ozogamicin

    Biological/Vaccine

    Given IV

  • Laboratory Biomarker Analysis

    Other intervention

    Correlative studies

  • Mercaptopurine

    Drug

    Given PO

  • Methotrexate

    Drug

    Given IT, IV, and PO

  • Prednisone

    Drug

    Given PO

  • Rituximab

    Biological/Vaccine

    Given IV

  • Vincristine

    Drug

    Given IV

Treatment groups

276 Participants
are divided into 3 treatment groups
Group A: Arm I (inotuzumab ozogamicin, combination chemotherapy)Experimental treatment 11 interventions
Group B: Arm II (inotuzumab ozogamicin, combination chemotherapy)Experimental treatment 11 interventions
Group C: Arm III (inotuzumab ozogamicin, combination chemotherapy)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose of inotuzumab ozogamicin based on incidence of dose limiting toxicities (Phase I)

Defined as non-hematologic grade 3 or 4 toxicities during the first course. Toxicities will be monitored using the method of Thall, Simon, and Estey. Adverse events will be summarized and toxicity rate will be estimated with a 90% credible interval.

Time frame
28 days
2

Progression free survival (PFS) in frontline elderly acute lymphoblastic leukemia (ALL) (Phase II)

Bayesian time-to-event model will be used. Kaplan and Meier product limit method will be used to estimate the PFS along with the 95% confidence intervals for the median PFS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.

Time frame
2 years
3

Response rate in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)

The precise complete remission (CR) and marrow CR rate will be defined.

Time frame
Up to 5 years
4

Survival in refractory-relapsed acute lymphoblastic leukemia (ALL) (Phase II)

The median and 1-year survival rate will be defined. Kaplan and Meier product limit method will be used to estimate the overall survival (OS) along with the 95% confidence intervals for the median OS. Univariate and multivariate Cox proportional hazards regression models will be used to identify prognostic factors.

Time frame
Up to 1 year

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

M.D. Anderson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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