HM2014-26 DT2219 for Relapsed or Refractory B-Lineage Leukemia or Lymphoma

Study Overview
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Brief Summary
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This is a phase I/II study of DT2219 for the treatment of relapsed or refractory CD19 (+) and/or CD 22 (+) B-lineage leukemia and lymphoma. The study consists of two phases - a phase I dose/schedule finding component using the maximum tolerated dose identified during the previous phase I study, but with a higher number of doses and a two-stage phase II extension component to confirm safety and make a preliminary determination of the activity level by disease using the dose identified in phase I.

Official Title
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HM2014-26 DT2219 Immunotoxin for the Treatment of Relapsed or Refractory CD19 (+) and/or CD 22 (+) B-lineage Leukemia or Lymphoma

Conditions
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Refractory B-Lineage Leukemia, Relapsed B-Lineage Leukemia, Refractory B-Lineage Lymphoma, Relapsed B-Lineage Lymphoma

Intervention / Treatment
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* Biological: DT2219ARL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic verification of B-cell lineage leukemia or B cell non-Hodgkin lymphoma and evidence of relapse/refractory disease with the presence of CD19 and/or CD22 by flow cytometry or immunohistochemistry of bone marrow aspirate, peripheral blood or node/tumor biopsy Relapsed refractory disease that has failed conventional therapy and other therapies of higher priority Karnofsky Performance status of ≥ 60% or, if less than 16 years of age, Lansky Play Score of ≥ 60 (appendix II) Recovered from effects of prior therapy Peripheral blast count under 50 x 10^9/L Adequate organ function within 14 days (30 days for cardiac and pulmonary) of treatment start Women of childbearing potential and men should be advised and agree to practice effective methods of contraception during the course of study Voluntary written consent with appropriate parent/guardian consent and minor information sheet for participants < 18 years of age Exclusion Criteria: Presence of leukemic or infectious pulmonary parenchymal disease Presence of active CNS leukemia Presence of any uncontrolled systemic infection Documented uncontrolled seizure disorder- a seizure disorder controlled with medication Active neurologic disorder - peripheral neuropathy alone does not exclude a patient Active Hepatitis B or Hepatitis C (virus detectable by PCR) Documented penicillin or cephalosporin allergies Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DT2219ARL<br>A recombinant bispecific antibody-targeted toxin. | Biological: DT2219ARL<br>* DT2219ARL at assigned dose IV on day 1, 3, 5, 8 and day 15, 17, 19, and 22. Up to 2 additional courses of DT2219ARL may be given until disease progression and/or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle | Dose limiting toxicity (DLT) is defined as any of the following adverse events occurring from study day 1 through 7 days after the last dose of DT2219 of the 1st treatment cycle, and not clearly attributed to the primary malignancy or intercurrent illness: any Grade 5 adverse event any Grade 4 neutropenia or thrombocytopenia lasting more for than 7 days any Grade 3 thrombocytopenia with bleeding any Grade 4 non-hematologic adverse event during DT2219 infusion any Grade 3 non-hematologic adverse event occurring after completion of DT2219 infusion | Day 1 - Day 29 | 
| Phase ll: Overall Disease Response | Response is defined as complete response, partial response and stable disease. Complete response is defined as the disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Partial response is defined as a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Stable disease is defined as cancer that is neither decreasing nor increasing in extent or severity. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Serious Adverse Events | A Serious Adverse Event is defined as an adverse event that results in any of the following outcomes: Death A life-threatening adverse event Inpatient hospitalization or prolongation of existing hospitalization A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions A congenital anomaly/birth defect. Important medical event | Day 29 | 
| Phase II : Duration of Response | Duration of response was calculated as duration between on-study date and best response date for those patients who achieved complete remission (CR) or partial response (PR) | 1 year | 
| Disease-free Survival |  | 1 year | 
| Overall Survival |  | 1 year | 
| Time to Relapse/Progression |  | 1 year |