Relapse Prophylaxis With N-803 for AML and MDS Pts Following Allo HSCT

Myelodysplastic Syndrome (MDS) Clinical Trial

Official title:

Relapse Prophylaxis With IL-15 Super Agonist N-803 in Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome Following Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02989844
• Other study ID #: 2016LS058
• Secondary ID: MT2016-07
• Status: Completed
• Phase: Phase 2
• Start date: April 12, 2017
• Est. completion date: August 31, 2022

Study information

• Verified date: October 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm, multi-center Phase II trial using IL-15 super-agonist complex (N-803 formerly known as Alt-803) maintenance after allogeneic hematopoietic cell transplant (alloHCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 31, 2022
• Est. primary completion date: March 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) for whom an allogeneic hematopoietic stem cell transplant using a reduced intensity conditioning is planned or has been performed and patient is prior to day 60 post-transplant.

2. Able to begin study treatment between day +42 and day +60 after the transplant and meets the following transplant related requirements:

• Sustained neutrophil (ANC > 1000/mcL) and platelet (> 30,000/mcL) engraftment

• >50% donor myeloid and lymphoid chimerism blood or bone marrow on most recent bone marrow (BM) evaluation

• No evidence of recurrent disease on most recent bone marrow evaluation (day 21 or 28 post-transplant is acceptable)

• No morphologic evidence of relapse (< 5% bone marrow blasts) on most recent BM evaluation (Day 21 or 28 post-transplant is acceptable)

• Being followed in the outpatient setting (not an inpatient)

• No plan of giving other anti-cancer treatment directed at diseases under study (i.e. maintenance therapy [e.g. sorafenib for FLT3m+ AML or hypomethylating therapy], additional therapy for MRD)

3. If acute GVHD is present it must be clinically improving on topical steroids and/or on low dose systemic steroids (= 0.3 mg/kg/day prednisone) and with clinical stability for at least 1 week prior to determination of eligibility. GVHD prophylaxis will be continued per individual institutional standard practice

4. One of the following donor graft sources used for the transplant:

• Group 1: sibling donor

• Group 2: haploidentical donor [with post-transplant cyclophosphamide]

• Group 3: unrelated donor

• Group 4: unrelated umbilical cord blood

5. Karnofsky performance status = 70%

6. Adequate organ function within 14 days of study enrollment defined as:

• Renal: serum creatinine: = 2.0 mg/dL

• Hepatic: SGOT = 3 x upper limit of institutional normal (ULN)

7. Sexually active females of child-bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy.

8. Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria:

1. Prior N-803 (previously known as ALT-803)

2. Pregnant or breastfeeding - N-803 is an investigational agent. Women of child bearing potential must have a negative pregnancy test at screening.

3. Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)

4. Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval > 500 milliseconds)

5. Active uncontrolled bacterial, fungal, or viral infections - all prior infections must have resolved following optimal therapy and must be afebrile for at least 24 hours at time of enrollment.

6. Active autoimmune disease requiring immunosuppressive therapy (GVHD prophylaxis is permitted per institutional practice)

7. History of severe asthma and currently on chronic medications (mild asthma requiring inhaled steroids only is eligible)

8. Received any investigational agent within the 14 days before the start of study treatment (1st dose of N-803)

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• N-803
N-803 at 6 mcg/kg SQ Day 1 of a 4 week (28 day) cycle with ± 1 week window Continue N-803 every 4 weeks for 10 doses or until relapse, unacceptable toxicity, or patient refusal, whichever comes earlier.

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Relapse	Efficacy of N-803 as measured by the cumulative incidence of relapse between the 1st dose of N-803 and 2 years after a reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplant (alloHCT)	24 months
Secondary	Incidence of Adverse Events	Frequency of all adverse	12 months
Secondary	Incidence of Acute Graft-versus-host Disease	Incidence of grade 2-4 and grade 3-4 acute graft-versus-host-disease (GVHD)	Day 100
Secondary	Incidence of Acute Graft-versus-host Disease	Incidence of grade 2-4 and grade 3-4 acute graft-versus-host-disease (GVHD)	Day 180
Secondary	Chronic GVHD	Incidence of acute graft-versus-host disease	1 year
Secondary	Minimal Residual Disease (MRD)	Incidence of minimal residual disease (MRD) post-transplant	1 year
Secondary	Overall Survival	Incidence of overall survival at one year	1 year post transplant
Secondary	Non-Relapse Mortality	Incidence of non-relapse mortality	1 year
Secondary	Relapse	Incidence of relapse at 2 years after alloHCT stratified by number of doses of N-803 (1-3 or 4-10)	2 Years