DT2219ARL for Relapsed or Refractory CD19 (+), CD 22 (+) B-Lineage Leukemia Or Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00889408
First received: April 26, 2009
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Leukemia
Lymphoma
Biological: DT2219ARL
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 36
Study Start Date: April 2009
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
DT2219ARL at assigned dose IV over 4 hours in the outpatient setting on day 1, 3, 5, and 8
Biological: DT2219ARL
anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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
  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00889408

Contacts
Contact: Dixie L Lewis, RN 612-624-4601 lewis029@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Dixie L Lewis, RN    612-624-4601    lewis029@umn.edu   
Principal Investigator: Veronika Bachanova, MD         
United States, Texas
M. D. Anderson Cancer Center at University of Texas Terminated
Houston, Texas, United States, 77030-4009
Scott and White Cancer Institute Terminated
Temple, Texas, United States, 76508
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Verokina Bachanova, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00889408     History of Changes
Other Study ID Numbers: 2012LS075, MT2013-16, DT2219ARL
Study First Received: April 26, 2009
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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
recurrent adult grade III lymphomatoid granulomatosis
Waldenström macroglobulinemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 20, 2014