## Protocol Section
### Identification Module
**NCT ID:** NCT00397579

**Brief Title:** DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

**Official Title:** Therapy Targeting the Interleukin-3 Receptor (IL3R) for Patients With Relapsed or Refractory and Elderly or Poor-Risk Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome With DTIL3 (IND# 11314): a Phase I/II Clinical Trial

#### Organization Study ID Info
**ID:** STU 012013-061
#### Organization
**Class:** OTHER
**Full Name:** University of Texas Southwestern Medical Center
### Status Module
#### Completion Date
**Date:** 2017-07-27

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-04-23

**Type:** ACTUAL

**Last Update Submit Date:** 2019-03-29

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2017-07-27

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2019-04-23

**Type:** ACTUAL

**Results First Submit Date:** 2018-11-21

**Results First Submit QC Date:** 2019-03-29

#### Start Date
**Date:** 2013-05

**Status Verified Date:** 2019-03

#### Study First Post Date
**Date:** 2006-11-09
**Type:** ESTIMATED
**Study First Submit Date:** 2006-11-08
**Study First Submit QC Date:** 2006-11-08
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Texas Southwestern Medical Center

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** RATIONALE: Combinations of biological substances in DT388IL3 fusion protein may be able to carry cancer killing substances directly to the cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of DT388IL3 fusion protein and to see how well it works in treating patients with acute myeloid leukemia or myelodysplastic syndromes.

**Detailed Description:** OBJECTIVES:

* Determine the maximum tolerated dose of DT_388IL3 fusion protein in patients with refractory or relapsed or poor-risk acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS).
* Define the dose-limiting toxicities of this regimen in these patients.
* Measure the pharmacokinetics of this regimen in these patients.
* Measure the immune responses in patients treated with this regimen.
* Evaluate response and correlate with disease type (relapsed/refractory or poor-risk de novo AML or high-risk MDS), pretreatment marrow blast percentage, and leukemia blast interleukin-3 receptor density.

OUTLINE: This is a phase I, multicenter, dose-escalation study followed by a phase II, open-label study.

* Phase I: Patients receive DT_388IL3 IV over 15 minutes daily for 5 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of DT_388IL3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase II: An additional 15 patients receive DT_388IL3 at the MTD as in phase I. Patients undergo serum and blast collection periodically for laboratory studies, including analysis of expression of interleukin-3 receptors and anti-DT_388IL3 antibodies at baseline. Samples are also analyzed by immunoenzyme assays and flow cytometry.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

### Conditions Module

**Conditions:**

- Leukemia

- Myelodysplastic Syndromes

- Blastic Plasmacytoid Dendritic Cell Neoplasm

**Keywords:**

- 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

- secondary acute myeloid leukemia

- untreated adult acute myeloid leukemia

- de novo myelodysplastic syndromes

- previously treated myelodysplastic syndromes

- secondary myelodysplastic syndromes

- blastic plasmacytoid dendritic cell neoplasm

- plasmacytoid dendritic cell leukemia

- CD123+

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 11

**Type:** ACTUAL

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

**Intervention Names:**

- Drug: DT388IL3

**Label:** SL-401

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- SL-401

**Description:** Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

**Name:** DT388IL3

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

Response to Treatment will be evaluated as follows:

Complete response (CR): patient has a normal whole blood count; platelets with absent blasts in peripheral blood or marrow; no evidence of nodal involvement or liver/spleen involvement; no skin lesion involvement.

Partial Response (PR); patient experiences a decrease of 50% or more in marrow blasts and skin lesions; and there is a decrease in the size of the nodes/liver/spleen.

Stable Disease (SD); failure to achieve at least PR, and there is no evidence of progression for 2 months.

Failure: death during treatment or disease progression characterized by an increase in the percentage bone marrow blast or an increase in skin or node/liver or spleen size.

Reported is the percentage of participants experiencing either CR, PR or SD.

**Measure:** Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response

**Time Frame:** From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months

### Eligibility Module

**Eligibility Criteria:** DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following:

  * Histologically or morphologically confirmed acute myeloid leukemia (AML), meeting 1 of the following criteria:

    * Relapsed or refractory AML after treatment with ≥ 1 prior conventional induction therapy

      * Patients in early first relapse must not have a matched donor available and/or be ineligible for allogeneic stem cell transplantation
    * Poor-risk AML, as defined by any of the following criteria:

      * Treatment-related AML, unless associated with favorable cytogenetics (e.g., inversion 16, t\[16;16\], t\[8;21\], t\[15;17\]), and ineligible for stem cell transplantation
      * Antecedent hematological disease (e.g., myelodysplastic syndromes, myelofibrosis, or polycythemia vera) that evolved to AML (≥ 20% blasts) and ineligible for stem cell transplantation
      * De novo AML (must be \> 70 years of age)
      * AML with unfavorable cytogenetics (e.g., abnormalities of chromosomes -7, -5, 7q-, or 5q-; complex \[≥ 3\] abnormalities; or abnormalities of 11q23, excluding t\[9;11\], t\[9;22\], inversion 3, t\[3;3\], and t\[6;9\]), regardless of age, and ineligible for allogeneic stem cell transplantation
  * High-risk myelodysplastic syndromes diagnosed by morphologic, histochemical, or cell surface marker criteria

    * Resistant or intolerant to chemotherapy
    * Ineligible for or unwilling to undergo immediate allogeneic stem cell transplantation
* Bone marrow index (i.e., percent cellularity × percent blasts) ≤ 40% at time of treatment
* No active CNS leukemia

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Bilirubin ≤ 1.5 mg/dL
* ALT and AST \< 2.5 times upper limit of normal
* Albumin ≥ 3 mg/dL
* Creatinine ≤ 1.5 mg/dL
* LVEF ≥ 50%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 2 weeks after completion of study treatment
* No complicated medical or psychiatric problems that would preclude study compliance
* No concurrent serious uncontrolled infection or disseminated intravascular coagulation
* No myocardial infarction within the past 6 months
* No allergies to diphtheria toxin
* No requirement for oxygen

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No other concurrent antineoplastic drugs
* No concurrent radiotherapy
* No concurrent corticosteroids as antiemetics
* No concurrent hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim \[G-CSF\], or sargramostim \[GM-CSF\])
* No concurrent intravenous immunoglobins

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Dallas

**Country:** United States

**Facility:** UT Southwestern Medical Center

**State:** Texas

**Zip:** 75390

#### Overall Officials

**Official 1:**

**Affiliation:** UT Southwestern Medical Center

**Name:** Arthur E. Frankel, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Frankel AE, Woo JH, Ahn C, Pemmaraju N, Medeiros BC, Carraway HE, Frankfurt O, Forman SJ, Yang XA, Konopleva M, Garnache-Ottou F, Angelot-Delettre F, Brooks C, Szarek M, Rowinsky E. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014 Jul 17;124(3):385-92. doi: 10.1182/blood-2014-04-566737. Epub 2014 May 23.

**PMID:** 24859366

## Document Section

### Large Document Module

#### Large Docs

- Date: 2016-11-22

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 247246

- Type Abbrev: Prot_SAP

- Upload Date: 2018-11-19T13:14

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000001855

- Term: Bone Marrow Diseases

- ID: D000011230

- Term: Precancerous Conditions

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: M18127

- Name: Leukemia, Myeloid, Acute

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: LOW

- As Found: Unknown

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M14164

- Name: Preleukemia

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: M12145

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14111

- Name: Precancerous Conditions

- Relevance: LOW

- As Found: Unknown

- ID: T3995

- Name: Myeloid Leukemia

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: T182

- Name: Acute Myeloid Leukemia

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: T188

- Name: Acute Non Lymphoblastic Leukemia

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T3993

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: T1792

- Name: Dendritic Cell Tumor

- Relevance: HIGH

- As Found: Dendritic Cell Neoplasm

- ID: T773

- Name: Blastic Plasmacytoid Dendritic Cell

- Relevance: HIGH

- As Found: Blastic Plasmacytoid Dendritic Cell

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000007951

- Term: Leukemia, Myeloid

- ID: D000015470

- Term: Leukemia, Myeloid, Acute

- ID: D000011289

- Term: Preleukemia

- ID: D000009190

- Term: Myelodysplastic Syndromes

- ID: D000013577

- Term: Syndrome

### Misc Info Module

#### Removed Countries

- Country: Canada

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** SL-401

**Deaths Num At Risk:** 11

**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

DT388IL3: Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

**ID:** EG000

**Other Num Affected:** 11

**Other Num at Risk:** 11

**Serious Number At Risk:** 11

**Title:** SL-401

**Frequency Threshold:** 0

#### Other Events

**Term:** AST

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Hepatobiliary disorders

**Source Vocabulary:** 

**Term:** Neutropenia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** ALT

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Hepatobiliary disorders

**Source Vocabulary:** 

**Term:** Thrombocytopenia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Hyponatremia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Time Frame:** 10 days

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 11

**Units:** Participants

### Group

**ID:** BG000

**Title:** SL-401

**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

DT388IL3: Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** <=18 years

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Between 18 and 65 years

#### Measurement

**Group ID:** BG000

**Value:** 10

**Category Title:** >=65 years

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Lower Limit:** 40

**Upper Limit:** 77

**Value:** 68

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 11

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 11

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 11

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Age, Categorical
**Unit of Measure:** Participants
### Measure 2
**Dispersion Type:** FULL_RANGE
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
**Population Description:** Patients with BPDCN treated with SL-401.
## Results Section - More Information Module
### Certain Agreement
**PI Sponsor Employee:** True
### Point of Contact
**Email:** studyfinder@utsouthwestern.edu
**Organization:** University of Texas Southwestern Medical Center at Dallas
**Phone:** 214-648-7097
**Title:** Clinical Research Office
## Results Section - Outcome Measures Module
### Outcome Measure 1
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 81.8
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

Response to Treatment will be evaluated as follows:

Complete response (CR): patient has a normal whole blood count; platelets with absent blasts in peripheral blood or marrow; no evidence of nodal involvement or liver/spleen involvement; no skin lesion involvement.

Partial Response (PR); patient experiences a decrease of 50% or more in marrow blasts and skin lesions; and there is a decrease in the size of the nodes/liver/spleen.

Stable Disease (SD); failure to achieve at least PR, and there is no evidence of progression for 2 months.

Failure: death during treatment or disease progression characterized by an increase in the percentage bone marrow blast or an increase in skin or node/liver or spleen size.

Reported is the percentage of participants experiencing either CR, PR or SD.
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months
**Title:** Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response
**Type:** PRIMARY
**Unit of Measure:** percentage of participants
##### Group
**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

DT388IL3: Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.
**ID:** OG000
**Title:** SL-401
### Participant Flow Module
#### Group
**Description:** Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

DT388IL3: Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.
**ID:** FG000
**Title:** SL-401
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 11
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 11
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
**Has Results:** True