NCT00889408

Brief 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. 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1 leukemia

Timeline
Completed

Started Dec 2013

Shorter than P25 for phase_1 leukemia

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 26, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 28, 2009

Completed
4.6 years until next milestone

Study Start

First participant enrolled

December 2, 2013

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 21, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 21, 2014

Completed
Last Updated

December 2, 2017

Status Verified

November 1, 2017

Enrollment Period

8 months

First QC Date

April 26, 2009

Last Update Submit

November 29, 2017

Conditions

LeukemiaLymphoma

Keywords

refractory chronic lymphocytic leukemiachildhood diffuse large cell lymphomachildhood grade III lymphomatoid granulomatosischildhood immunoblastic large cell lymphomaB-cell adult acute lymphoblastic leukemiarecurrent adult acute lymphoblastic leukemiaB-cell childhood acute lymphoblastic leukemiarecurrent childhood acute lymphoblastic leukemiaadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult 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 leukemiarecurrent childhood acute myeloid leukemiasecondary acute myeloid leukemiaB-cell chronic lymphocytic leukemiarelapsing chronic myelogenous leukemiachildhood chronic myelogenous leukemiacutaneous B-cell non-Hodgkin lymphomarecurrent adult grade III lymphomatoid granulomatosisWaldenström macroglobulinemiarecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomarecurrent childhood grade III lymphomatoid granulomatosisrecurrent childhood large cell lymphomarecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomachildhood Burkitt lymphomaintraocular lymphomanoncutaneous extranodal lymphomaprolymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

  • 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).

    29 days

Secondary Outcomes (1)

  • Therapeutic activity of DT2219ARL

    2 years

Study Arms (1)

Treatment

EXPERIMENTAL

DT2219ARL at assigned dose IV over 4 hours in the outpatient setting on day 1, 3, 5, and 8

Biological: DT2219ARL

Interventions

DT2219ARLBIOLOGICAL

anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL

Treatment

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Scott and White Cancer Institute

Temple, Texas, 76508, United States

Location

MeSH Terms

Conditions

LeukemiaLymphomaLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large B-Cell, DiffusePrecursor Cell Lymphoblastic Leukemia-LymphomaCongenital AbnormalitiesLeukemia, Myeloid, AcuteWaldenstrom MacroglobulinemiaBurkitt LymphomaLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneDendritic Cell Sarcoma, InterdigitatingIntraocular LymphomaLeukemia, Prolymphocytic

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, MyeloidNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsHistiocytic Disorders, MalignantHistiocytosisEye NeoplasmsNeoplasms by Site

Study Officials

  • Verokina Bachanova, MD

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 26, 2009

First Posted

April 28, 2009

Study Start

December 2, 2013

Primary Completion

July 21, 2014

Study Completion

July 21, 2014

Last Updated

December 2, 2017

Record last verified: 2017-11

Locations

US(3)