DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SL-401 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. |
Drug: DT388IL3
Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response [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]
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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
Investigators
- Principal Investigator: Arthur E. Frankel, MD, UT Southwestern Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- STU 012013-061
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SL-401 |
|---|---|
| Arm/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. |
| Period Title: Overall Study | |
| STARTED | 11 |
| COMPLETED | 11 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | SL-401 |
|---|---|
| Arm/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. |
| Overall Participants | 11 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
1
9.1%
|
| >=65 years |
10
90.9%
|
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
68
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
11
100%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
11
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
11
100%
|
Outcome Measures
| Title | Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response |
|---|---|
| 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SL-401 |
|---|---|
| Arm/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. |
| Measure Participants | 11 |
| Number [percentage of participants] |
81.8
743.6%
|
Adverse Events
| Time Frame | 10 days | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | SL-401 | |
| Arm/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. | |
All Cause Mortality |
||
| SL-401 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | |
Serious Adverse Events |
||
| SL-401 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| SL-401 | ||
| Affected / at Risk (%) | # Events | |
| Total | 11/11 (100%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 1/11 (9.1%) | 1 |
| Thrombocytopenia | 4/11 (36.4%) | 4 |
| Hyponatremia | 1/11 (9.1%) | 1 |
| Hepatobiliary disorders | ||
| AST | 4/11 (36.4%) | 4 |
| ALT | 3/11 (27.3%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Clinical Research Office |
|---|---|
| Organization | University of Texas Southwestern Medical Center at Dallas |
| Phone | 214-648-7097 |
| studyfinder@utsouthwestern.edu |
- STU 012013-061