Refractory B-Lineage Leukemia, Refractory B-Lineage Lymphoma, Relapsed B-Lineage Leukemia, Relapsed B-Lineage Lymphoma
Conditions
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.
Interventions
BIOLOGICALDT2219ARL
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.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse/Progression | 1 year | — |
| Disease-free Survival | 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) |
| 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 |
| Overall Survival | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DT2219ARL A recombinant bispecific antibody-targeted toxin.
DT2219ARL: 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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 1 |
Baseline characteristics
| Characteristic | DT2219ARL |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 68.11 years STANDARD_DEVIATION 7.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 18 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 9 | 4 / 6 | 1 / 3 |
| other Total, other adverse events | 9 / 9 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 2 / 9 | 2 / 6 | 1 / 3 |
Outcome results
Primary
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
Time frame: Day 1 - Day 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle | 1 events |
| DT2219 80 µg/kg/Dose (Phase I) | Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle | 3 events |
| DT2219 (Phase II) | Phase I: Incidence of Any DLT Attributed to DT2219 in the First Cycle | 0 events |
Primary
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.
Time frame: Day 29
Population: 12 Subjects treated on dose level 1: 4 achieved stable disease and 1 had partial response
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Phase ll: Overall Disease Response | 5 Participants |
Secondary
Disease-free Survival
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Disease-free Survival | 7 Participants |
| DT2219 80 µg/kg/Dose (Phase I) | Disease-free Survival | 5 Participants |
| DT2219 (Phase II) | Disease-free Survival | 3 Participants |
Secondary
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
Time frame: Day 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Incidence of Serious Adverse Events | 2 events |
| DT2219 80 µg/kg/Dose (Phase I) | Incidence of Serious Adverse Events | 2 events |
| DT2219 (Phase II) | Incidence of Serious Adverse Events | 1 events |
Secondary
Overall Survival
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Overall Survival | 3 Participants |
| DT2219 80 µg/kg/Dose (Phase I) | Overall Survival | 4 Participants |
| DT2219 (Phase II) | Overall Survival | 2 Participants |
Secondary
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)
Time frame: 1 year
Population: Only 2 participants achieved CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Phase II : Duration of Response | 59.5 days |
Secondary
Time to Relapse/Progression
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DT2219ARL 60 µg/kg/Dose (Phase I) | Time to Relapse/Progression | 27.3 days |
| DT2219 80 µg/kg/Dose (Phase I) | Time to Relapse/Progression | 42 days |
| DT2219 (Phase II) | Time to Relapse/Progression | 30 days |