QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT03050216
Collaborator
(none)
8
1
1
31
0.3

Study Details

Study Description

Brief Summary

This is a multi-institutional Simon's optimal two-stage phase II trial of CD3/CD19 depleted, ALT-803 activated, haploidentical donor NK cells and subcutaneous ALT-803 given after lymphodepleting chemotherapy (CY/FLU) for the treatment of refractory or released acute myelogenous leukemia (AML).

Condition or Disease Intervention/Treatment Phase
  • Biological: ALT-803
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
QUILT-3.033: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous ALT-803 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia
Actual Study Start Date :
May 16, 2017
Actual Primary Completion Date :
Dec 15, 2019
Actual Study Completion Date :
Dec 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cy, FLU, Haplo NK and ALT-803

Preparative Regimen of Fludarabine and Cyclophosphamide ALT-803 Activation of Donor NK Cells ALT-803 to Facilitate NK Cell Survival and Expansion

Biological: ALT-803
Preparative Regimen: Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 ALT-803 Stimulated Donor NK Cells: The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be stimulated by overnight incubation with 36.1 ng/mL ALT-803 under GMP conditions and infused on day 0. ALT-803 to Facilitate NK Cell Survival and Expansion: ALT-803 at 10 mcg/kg subcutaneously (SC) with the 1st dose administered on day 0 (no sooner than 4 hours post NK cells), day +5 and day +10 for 3 doses total

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery [Day 42 post NK cell infusion]

    To estimate the rate of complete remission with incomplete platelet recovery (CRp) - defined as leukemic clearance and neutrophil recovery without platelet recovery - by day 42 after the infusion of CD3/CD19 depleted, ALT-803 stimulated, donor NK cells and subcutaneous ALT-803 given after a non-myeloablative preparative regimen for the treatment of refractory or released acute myelogenous leukemia (AML)

Secondary Outcome Measures

  1. Incidence of in Vivo Expansion ≥100 of Donor Derived NK Cells Per /μl Blood [Day 14 post NK cell infusion]

    Number of patients with successful in vivo NK-cell expansion which is defined by measuring an absolute circulating donor-derived NK cell count of ≥100 cells/μl in patient's peripheral blood.

  2. Number of Participants Experiencing ALT-803 Associated Toxicity [Day 0]

    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)

  3. Number of Participants Experiencing ALT-803 Associated Toxicity [Day 5]

    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)

  4. Number of Participants Experiencing ALT-803 Associated Toxicity [Day 7]

    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)

  5. Number of Participants Experiencing ALT-803 Associated Toxicity [Day 10]

    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)

  6. Number of Participants With Treatment Related Mortality [6 months post-therapy]

    To evaluate the safety of the therapy as measured by rate of treatment related mortality (TRM) at 6 months

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:

  • Primary induction failure:

  • De novo AML - no CR after 2 or more chemotherapy induction attempts

  • Secondary AML (from MDS or treatment related): no CR after 1 or more chemotherapy induction attempts

  • Relapse after chemotherapy: not in CR after 1, 2, or 3 re-induction attempts

  • Patients > 60 years of age, the 1 cycle of chemotherapy is not required

  • Relapse after hematopoietic stem cell transplant:

  • Relapse must have occurred > 18 months after transplant

  • No re-induction required and no more than 1 re-induction attempt is allowed

  • Notes:

  1. For hypomethylating agents (i.e. decitabine, azacitidine) to count as an induction/re-induction attempt, the patient must have completed a minimum of 3 monthly cycles

  2. For targeting agents (i.e. sorafenib) to count as an induction/re-induction attempt, the patient must have completed a minimum of 1 month without attaining CR

  3. 7+3 followed by 5+2 counts as TWO induction attempts

  4. Use of hydroxyurea is permitted to control blasts until Day -3 per Section 8.7

  5. A history of AML related CNS involvement is allowed if CSF analysis is negative on 2 test dates at least 2 weeks apart prior to study treatment. The use of ongoing CNS maintenance therapy is allowed while on study.

  • HLA-haploidentical related donor (aged 12 to 75 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A and B locus (at least 2/4 class I allele)

  • Karnofsky Performance Status ≥ 60%

  • Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:

  • Creatinine: ≤ 2.0 mg/dL

  • Hepatic: AST and ALT < 3 x upper limit of institutional normal

  • Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function >50% corrected DLCO and FEV1.

  • Cardiac Function: LVEF ≥ 40% by echocardiography, MUGA or cardiac MRI, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

  • Able to be off prednisone or other systemic immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications) .

  • 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 .

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

Exclusion Criteria:
  • Acute leukemias of ambiguous lineage

  • Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test at screening

  • Active autoimmune disease requiring systemic immunosuppressive therapy

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

  • New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).

  • Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed

  • Received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)

  • Prior ALT-803

Contacts and Locations

Locations

Site City State Country Postal Code
1 Masonic Cancer Center at University of Minnesota Minneapolis Minnesota United States 55455

Sponsors and Collaborators

  • Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Claudio Brunstein, MD, PhD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT03050216
Other Study ID Numbers:
  • 2016LS056
  • MT2016-05
First Posted:
Feb 10, 2017
Last Update Posted:
Nov 27, 2020
Last Verified:
Oct 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Period Title: Overall Study
STARTED 8
COMPLETED 8
NOT COMPLETED 0

Baseline Characteristics

Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Overall Participants 8
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
7
87.5%
>=65 years
1
12.5%
Sex: Female, Male (Count of Participants)
Female
3
37.5%
Male
5
62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
Not Hispanic or Latino
8
100%
Unknown or Not Reported
0
0%
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
8
100%
More than one race
0
0%
Unknown or Not Reported
0
0%
Region of Enrollment (participants) [Number]
United States
8
100%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery
Description To estimate the rate of complete remission with incomplete platelet recovery (CRp) - defined as leukemic clearance and neutrophil recovery without platelet recovery - by day 42 after the infusion of CD3/CD19 depleted, ALT-803 stimulated, donor NK cells and subcutaneous ALT-803 given after a non-myeloablative preparative regimen for the treatment of refractory or released acute myelogenous leukemia (AML)
Time Frame Day 42 post NK cell infusion

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
1
12.5%
2. Secondary Outcome
Title Incidence of in Vivo Expansion ≥100 of Donor Derived NK Cells Per /μl Blood
Description Number of patients with successful in vivo NK-cell expansion which is defined by measuring an absolute circulating donor-derived NK cell count of ≥100 cells/μl in patient's peripheral blood.
Time Frame Day 14 post NK cell infusion

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
0
0%
3. Secondary Outcome
Title Number of Participants Experiencing ALT-803 Associated Toxicity
Description Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
Time Frame Day 0

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
2
25%
4. Secondary Outcome
Title Number of Participants Experiencing ALT-803 Associated Toxicity
Description Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
Time Frame Day 5

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
1
12.5%
5. Secondary Outcome
Title Number of Participants Experiencing ALT-803 Associated Toxicity
Description Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
Time Frame Day 7

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
3
37.5%
6. Secondary Outcome
Title Number of Participants Experiencing ALT-803 Associated Toxicity
Description Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
Time Frame Day 10

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
3
37.5%
7. Secondary Outcome
Title Number of Participants With Treatment Related Mortality
Description To evaluate the safety of the therapy as measured by rate of treatment related mortality (TRM) at 6 months
Time Frame 6 months post-therapy

Outcome Measure Data

Analysis Population Description
One patient died after receiving 2 days of chemotherapy and never received any elements of research, NK cells or ALT-803. So only 7 participants' data were analyzed
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
Measure Participants 7
Count of Participants [Participants]
6
75%

Adverse Events

Time Frame 1 year
Adverse Event Reporting Description
Arm/Group Title Cy, FLU, Haplo NK and ALT-803
Arm/Group Description Fludarabine 25 mg/m2 x 5 days start Day -6 ; Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 ; The Alt-803 stimulated NK cell enriched product on Day 0 followed by ALT-803 at 10 mcg/kg subcutaneously on Day 0, Day 5 and Day 10
All Cause Mortality
Cy, FLU, Haplo NK and ALT-803
Affected / at Risk (%) # Events
Total 8/8 (100%)
Serious Adverse Events
Cy, FLU, Haplo NK and ALT-803
Affected / at Risk (%) # Events
Total 7/8 (87.5%)
Blood and lymphatic system disorders
Febrile neutropenia 2/8 (25%) 2
Febrile neutropenia - Changed to levaquin and micafungin 1/8 (12.5%) 1
Cardiac disorders
Heart failure 1/8 (12.5%) 1
Infections and infestations
Lung infection 1/8 (12.5%) 1
Metabolism and nutrition disorders
Tumor lysis syndrome 1/8 (12.5%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 5/8 (62.5%) 5
Renal and urinary disorders
Acute kidney injury 1/8 (12.5%) 1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 1/8 (12.5%) 1
Other (Not Including Serious) Adverse Events
Cy, FLU, Haplo NK and ALT-803
Affected / at Risk (%) # Events
Total 8/8 (100%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation 1/8 (12.5%) 1
Febrile neutropenia 4/8 (50%) 6
Cardiac disorders
Atrial fibrillation 1/8 (12.5%) 1
Gastrointestinal disorders
Constipation 1/8 (12.5%) 1
Diarrhea 1/8 (12.5%) 1
Oral pain 1/8 (12.5%) 1
Vomiting 1/8 (12.5%) 2
Gastroesophageal reflux disease 1/8 (12.5%) 1
General disorders
Chills 7/8 (87.5%) 11
Fatigue 4/8 (50%) 7
Fever 5/8 (62.5%) 17
Injection site reaction 7/8 (87.5%) 24
Pain 2/8 (25%) 4
Infusion related reaction 3/8 (37.5%) 3
Infections and infestations
Clostridium Difficile Infection 1/8 (12.5%) 1
Sepsis 1/8 (12.5%) 1
Investigations
Alanine aminotransferase increased 1/8 (12.5%) 1
Aspartate aminotransferase increased 1/8 (12.5%) 1
Blood bilirubin increased 1/8 (12.5%) 3
Urine output decreased 1/8 (12.5%) 1
Metabolism and nutrition disorders
Anorexia 1/8 (12.5%) 1
Hypoalbuminemia 1/8 (12.5%) 1
Hypocalcemia 1/8 (12.5%) 2
Hypophosphatemia 1/8 (12.5%) 1
Musculoskeletal and connective tissue disorders
Myalgia 1/8 (12.5%) 1
Generalized muscle weakness 1/8 (12.5%) 1
Nervous system disorders
Dizziness 2/8 (25%) 2
Headache 6/8 (75%) 12
Nervous system disorders - Other 1/8 (12.5%) 1
Psychiatric disorders
Anxiety 1/8 (12.5%) 1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 1/8 (12.5%) 1
Cough 1/8 (12.5%) 1
Dyspnea 1/8 (12.5%) 3
Hypoxia 2/8 (25%) 3
Skin and subcutaneous tissue disorders
Rash maculo-papular 1/8 (12.5%) 1
Skin and subcutaneous tissue disorders - Other 2/8 (25%) 2
Vascular disorders
Hypertension 4/8 (50%) 14
Hypotension 4/8 (50%) 6

Limitations/Caveats

[Not Specified]

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 Dr.Claudio G. Brunstein MD, PhD
Organization Masonic Cancer Center, University of Minnesota
Phone 612 625 3918
Email bruns072@umn.edu
Responsible Party:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT03050216
Other Study ID Numbers:
  • 2016LS056
  • MT2016-05
First Posted:
Feb 10, 2017
Last Update Posted:
Nov 27, 2020
Last Verified:
Oct 1, 2020