DT2219ARL for Relapsed or Refractory CD19 (+), CD 22 (+) 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).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Maximum tolerated dose [ Time Frame: 29 days ] [ Designated as safety issue: Yes ]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).
- Therapeutic activity of DT2219ARL [ Time Frame: 2 years ] [ Designated as safety issue: No ]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
|Study Start Date:||April 2009|
|Estimated Study Completion Date:||June 2016|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
DT2219ARL at assigned dose IV over 4 hours in the outpatient setting on day 1, 3, 5, and 8
anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00889408
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Texas|
|M. D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|Scott and White Cancer Institute|
|Temple, Texas, United States, 76508|
|Principal Investigator:||Verokina Bachanova, MD||University of Minnesota - Clinical and Translational Science Institute|