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

Phase 1

Completed

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

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
DT2219ARL	DT2219ARL	A recombinant bispecific antibody-targeted toxin.

Primary Outcome Measures

Name	Time	Method
Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle	Day 1 - Day 29	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
Phase ll: Overall Disease Response	Day 29	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	1 year
Disease-free Survival	1 year
Incidence of Serious Adverse Events	Day 29	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
Time to Relapse/Progression	1 year
Phase II : Duration of Response	1 year	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)