LeukemiaPhase 1NCT00889408
DT2219ARL for Relapsed or Refractory CD19 (+), CD 22 (+) B-Lineage Leukemia Or Lymphoma
A Phase 1 study testing DT2219ARL in people with Leukemia and Lymphoma, run by Masonic Cancer Center, University of Minnesota at 3 sites in United States.
Trial summary
This is a phase I dose escalation study of DT2219ARL for the treatment of relapsed or refractory B-lineage leukemia and lymphoma. Patients will receive a single course of DT2219ARL as a 4 hour infusion on days 1, 3, 5, and 8. Read more about this study
- Who is it for?
- Ages 12 years and older
- What is being tested?
- DT2219ARL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 Dec 2013to 21 Jul 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 biopsy
- Disease refractory to conventional therapy and other therapies of higher priority
- Age ≥ 12 years
- Karnofsky Performance status of ≥ 60% or, if less than 16 years of age, Lansky Play Score of ≥ 60 (appendix II)
- Patients must have recovered from effects of prior therapy - at least 2 weeks should have elapsed since the last dose of chemotherapy; however patients who have recovered from the effects of previous treatment and have a >50% rise in peripheral blast count (confirmed twice) or > 50% growth of lymph nodes are immediately eligible - Patients who have relapsed following autologous or allogeneic BMT are eligible
- In order to prevent tumor lysis syndrome, leukemia patients must have a peripheral blast count under 50 x 109/L. This should be achieved with hydroxyurea cytoreduction, prior to starting DT2219ARL as follows - patients with peripheral blasts and a WBC >50 x 109/L, give hydroxyurea 1-5 g daily for up to 5 days to reduce WBC below 50 x 109/L
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- Adequate organ function within 14 days (30 days for cardiac and pulmonary) of treatment start defined as:
- Creatinine: ≤ 1.5 x upper limit of institutional normal (ULN)
- Hepatic: SGOT (AST) or SGPT (ALT) < 2.5 x ULN and total bilirubin </= 1.5 x ULN
- General health: Serum albumin ≥ 3.0g/dL
- Pulmonary: PFTs > 50% if symptomatic or prior known impairment
- Cardiac: LVEF by ECHO or MUGA ≥ 40%
- Agrees to stay within the Twin Cities metropolitan area (i.e. within 30 miles of the study center) for the duration of the treatment (at least 24 hours after the last dose) and 2) have a capable caregiver
- 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
Who cannot join
- Presence of leukemic or infectious pulmonary parenchymal disease
- Presence of active CNS leukemia. CSF with <5 WBC/uL will not exclude the patient
- Presence of any uncontrolled systemic infection
- Documented uncontrolled seizure disorder or abnormal neurological examination - a seizure disorder controlled with medication (i.e. no seizures in the previous 6 months) will not exclude a patient
- Documented penicillin or cephalosporin allergies
- Pregnant or lactating - Women of child bearing potential must have a negative pregnancy test within 14 days of study treatment start
Trial locations and contacts
3 sites in 1 country.
United States3 sites
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Scott and White Cancer Institute
Temple, Texas, 76508
About this study
Official title: A Phase I Study of DT2219ARL, A Bispecific Singe Chain Immunotoxin for the Treatment of Relapsed or Refractory CD19(+), CD22(+) B-Lineage Leukemia or Lymphoma
This is a phase I dose escalation study of DT2219ARL for the treatment of relapsed or refractory B-lineage leukemia and lymphoma. Patients will receive a single course of DT2219ARL as a 4 hour infusion on days 1, 3, 5, and 8. Weekly follow-up will continue through day 29, at which time a disease reassessment will be done. For patients in remission, follow-up will continue monthly until disease progression or start of a new treatment. Otherwise day 29 will be the final study visit if there is no ongoing toxicity.
This phase I study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD) of DT2219ARL. Up to 3 dose levels will be tested with an additional dose level (-1) if dose level 1 proves too toxic. The goal of CRM is to identify the dose level which correspondences to a desired toxicity rate of 33% or less using grade 3 or 4 capillary leak syndrome and any grade 3 or greater toxicity attributed to DT2219ARL as the targeted toxicity (based on CTCAE version 4).
Read the detailed description
The current study was initially conducted at University of Texas and the Scott and White Cancer Institute (A. Frankel, MD - PI) and M. D. Anderson Cancer Center with 15 evaluable patients enrolled by the end of 2011 (table 1). The 3rd patient enrolled in the 40 μg/kg dose cohort was the first to experience dose limiting toxicity (grade 3 neurological: lower extremity weakness) receiving only 3 of the 4 planned doses. Per study design, the 40 μg/kg would enroll an additional 3 patients to confirm dose limiting toxicity. It is at this point the Texas centers discontinued involvement in the study.
Approximately 15 months after the last patient was enrolled under the original study plan, the protocol was redesigned by the Masonic Cancer Center at the University of Minnesota, building on the experience of the 1st 15 patients enrolled through the Texas centers. To increase efficiency, the study design was changed from the standard 3 x 3 dose escalation to a Continuous Reassessment Method (CRM) model testing 3 doses levels (40, 60, and 80 ug/kg) with an added feature of a dose level -1 (30 ug/kg) in the event dose level 1 proves too toxic. The maximum tolerated dose will be identified once 20 evaluable patients are enrolled.
- Being tested
- DT2219ARL
- Keywords
- refractory chronic lymphocytic leukemia, childhood diffuse large cell lymphoma, childhood grade III lymphomatoid granulomatosis, childhood immunoblastic large cell lymphoma, B-cell adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, B-cell chronic lymphocytic leukemia, relapsing chronic myelogenous leukemia, childhood chronic myelogenous leukemia, cutaneous B-cell non-Hodgkin lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Congenital Abnormalities, Leukemia, Myeloid, Acute, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DT2219ARLBiological
anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | DT2219ARL at assigned dose IV over 4 hours in the outpatient setting on day 1, 3, 5, and 8 Receives: Biological: DT2219ARL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
This phase I study will use Continual Reassessment method (CRM) method to establish a maximum tolerated dose (MTD) of DT2219ARL when the maximum desired level of toxicity is 33% (defined as grade 3 or 4 capillary leak syndrome toxicities and any grade 3 or greater adverse event attributed to DT2219ARL based on CTCAE v 4).
Measured: 29 days
Secondary outcomes (1)
Therapeutic activity of DT2219ARL
Determined by the change in percentage of blasts in bone marrow and peripheral blood and recovery of normal hematopoiesis and by change in size of lymph nodes/tumor involved by lymphoma
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2009 (estimated)
- Study start2 Dec 2013
- Primary completion21 Jul 2014
- Study completion21 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Verokina Bachanova, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00889408
- Sponsor's protocol ID
- 2012LS075
- Other IDs
- MT2013-16, DT2219ARL
- Status last verified
- Nov 2017
- First submitted
- 26 Apr 2009
- Last updated
- 2 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of DT2219ARL, A Bispecific Singe Chain Immunotoxin for the Treatment of Relapsed or Refractory CD19(+), CD22(+) B-Lineage Leukemia or Lymphoma
- ClinicalTrials.gov ID
- NCT00889408
- Acronym / sponsor ID
- 2012LS075
- Keywords
- refractory chronic lymphocytic leukemia, childhood diffuse large cell lymphoma, childhood grade III lymphomatoid granulomatosis, childhood immunoblastic large cell lymphoma, B-cell adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 2 Dec 2013 (actual)
- Primary completion
- 21 Jul 2014 (actual)
- Study completion
- 21 Jul 2014 (actual)
- First posted
- 28 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I dose escalation study of DT2219ARL for the treatment of relapsed or refractory B-lineage leukemia and lymphoma. Patients will receive a single course of DT2219ARL as a 4 hour infusion on days 1, 3, 5, and 8. Weekly follow-up will continue through day 29, at which time a disease reassessment will be done. For patients in remission, follow-up will continue monthly until disease progression or start of a new treatment. Otherwise day 29 will be the final study visit if there is no ongoing toxicity.
This phase I study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD) of DT2219ARL. Up to 3 dose levels will be tested with an additional dose level (-1) if dose level 1 proves too toxic. The goal of CRM is to identify the dose level which correspondences to a desired toxicity rate of 33% or less using grade 3 or 4 capillary leak syndrome and any grade 3 or greater toxicity attributed to DT2219ARL as the targeted toxicity (based on CTCAE version 4).
Detailed description
The current study was initially conducted at University of Texas and the Scott and White Cancer Institute (A. Frankel, MD - PI) and M. D. Anderson Cancer Center with 15 evaluable patients enrolled by the end of 2011 (table 1). The 3rd patient enrolled in the 40 μg/kg dose cohort was the first to experience dose limiting toxicity (grade 3 neurological: lower extremity weakness) receiving only 3 of the 4 planned doses. Per study design, the 40 μg/kg would enroll an additional 3 patients to confirm dose limiting toxicity. It is at this point the Texas centers discontinued involvement in the study.
Approximately 15 months after the last patient was enrolled under the original study plan, the protocol was redesigned by the Masonic Cancer Center at the University of Minnesota, building on the experience of the 1st 15 patients enrolled through the Texas centers. To increase efficiency, the study design was changed from the standard 3 x 3 dose escalation to a Continuous Reassessment Method (CRM) model testing 3 doses levels (40, 60, and 80 ug/kg) with an added feature of a dose level -1 (30 ug/kg) in the event dose level 1 proves too toxic. The maximum tolerated dose will be identified once 20 evaluable patients are enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: DT2219ARLDT2219ARL at assigned dose IV over 4 hours in the outpatient setting on day 1, 3, 5, and 8 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- 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 biopsy
- Disease refractory to conventional therapy and other therapies of higher priority
- Age ≥ 12 years
- Karnofsky Performance status of ≥ 60% or, if less than 16 years of age, Lansky Play Score of ≥ 60 (appendix II)
- Patients must have recovered from effects of prior therapy - at least 2 weeks should have elapsed since the last dose of chemotherapy; however patients who have recovered from the effects of previous treatment and have a >50% rise in peripheral blast count (confirmed twice) or > 50% growth of lymph nodes are immediately eligible - Patients who have relapsed following autologous or allogeneic BMT are eligible
Key exclusion criteria (6 listed)
- Presence of leukemic or infectious pulmonary parenchymal disease
- Presence of active CNS leukemia. CSF with <5 WBC/uL will not exclude the patient
- Presence of any uncontrolled systemic infection
- Documented uncontrolled seizure disorder or abnormal neurological examination - a seizure disorder controlled with medication (i.e. no seizures in the previous 6 months) will not exclude a patient
- Documented penicillin or cephalosporin allergies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DT2219ARLanti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL | Biological | Treatment |
Primary outcome
Maximum tolerated dose
Time frame: 29 days
This phase I study will use Continual Reassessment method (CRM) method to establish a maximum tolerated dose (MTD) of DT2219ARL when the maximum desired level of toxicity is 33% (defined as grade 3 or 4 capillary leak syndrome toxicities and any grade 3 or greater adverse event attributed to DT2219ARL based on CTCAE v 4).
1 secondary outcome
Therapeutic activity of DT2219ARL
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Verokina Bachanova, MD principal investigator
University of Minnesota
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DT2219ARL in people with Leukemia and Lymphoma, run by Masonic Cancer Center, University of Minnesota at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.