CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated In... | NCT04620681

ID	Type	Description	Link
G6095	Other Grant/Funding Number	FDA

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1 Dose Level 1	Experimental	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg	Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes Drug: Standard of Care Chemotherapy
Phase 1 Dose Level 2	Experimental	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10^7 CD4 T Cells/kg	Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes Drug: Standard of Care Chemotherapy
Phase 1 Dose Level 3	Experimental	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10^7 CD4 T Cells/kg	Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes Drug: Standard of Care Chemotherapy
Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes	Biological	Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose of CD8 Depleted Non-engrafting HLA-mismatched Unrelated Donor Lymphocytes Infusion (NE-DLI)	Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).	Up to 60 days per dose level

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate	Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.	Up to 12 months
Progression Free Survival	Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Myelodysplastic Syndrome (MDS) having failed hypomethylating agent (HMA) therapy cohort:

Age 18-79 years, inclusive
Pathologically confirmed MDS or myelodysplastic/myeloproliferative overlap (MDS/MPN)
IPSS-R score intermediate, high or very high
Must have failed therapy with an HMA (defined as lack of response by International Working Group criteria (1) or intolerance of the drug)

Secondary Acute Myeloid Leukemia (sAML):

Pathologically confirmed AML according to World Health Organization (WHO) criteria
Evidence of an antecedent hematologic disorder (AHD) prior to acute leukemia including a known prior diagnosis of MDS, MPN or MDS/MPN or data suggestive of an AHD such as cytopenias, fibrosis, macrocytic anemia, cellular or dysplasia at or prior to the time of diagnosis. If available, MDS-defining karyotypes (-7/del(7q), -5/del(5q), del(13q), del(11q), del(12p), t(12p), del(9q), idic(X)(q13), t(17p) (unbalanced translocations) or i(17q) (ie, loss of 17p), t(11;16)(q23;p13.3), t(3;21)(q26.2;q22.1), t(1;3)(p36.3;q21), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)) or somatic mutations in multiple genes including p53, TET2, JAK2, CALR, MPL, ASXL1, RUNX1, SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 would also confirm eligibility.
Age 60-79 years, inclusive
May be previously untreated

For both cohorts:

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Deemed eligible to receive cytotoxic chemotherapy
Creatinine clearance (CrCl)>50ml/min
Total bilirubin <2 mg/dL (except for patients with Gilbert's disease), AST and ALT < 3x ULN
Left Ventricular Ejection Fraction ≥ 50%
Willing and able to participate in study assessments

Exclusion Criteria:

Patients who have had systemic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Hydroxyurea during this period may be given as a bridging therapy to maintain disease stability while awaiting treatment. Intrathecal chemotherapy within this time frame is permitted. Intrathecal chemotherapy may be continued during protocol therapy in order to consolidate or maintain a central nervous system (CNS) remission, but not to treat active CNS disease
Acute promyelocytic leukemia, or the presence of t(15;17)
Patients receiving any other investigational agents
Uncontrolled concurrent illness including, but not limited to, ongoing and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the fetus. Breastfeeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study
Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up
Patients with a poor functional status of ECOG 3-4, or otherwise deemed unfit to tolerate induction chemotherapy.
Patients with blastic transformation of chronic myelogenous leukemia are ineligible
Exposure to a humanized mouse chimeric antibody, as this could sensitize patients to components of the CD8 depletion column that may be present in small amounts in the cell product
Prior allogenic hematopoietic cell transplant

Name	Affiliation	Role
Joseph Pidala, MD, PhD	Moffitt Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Moffitt Cancer Center		Tampa	Florida	33612	United States

Label	URL
Moffitt Cancer Center Clinical Trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase 1 Dose Level 1	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 29, 2023

Arm/Group Information

ID	Title	Description
BG000	Phase 1 Dose Level 1	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy
BG001	Phase 1 Dose Level 2	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10^7 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy
BG002	Phase 1 Dose Level 3	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10^7 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy
BG003	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at MTD. CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0013 BG0023 BG00310 BG00419

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose of CD8 Depleted Non-engrafting HLA-mismatched Unrelated Donor Lymphocytes Infusion (NE-DLI)

Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).

Posted

Number

10^7 CD4 cells/kg

Up to 60 days per dose level

ID	Title	Description
OG000	Maximum Tolerated Dose (MTD)	All participants from dose escalation phase who received treatment at either dose level 1, dose level 2, or dose level 3.

Units	Counts
Participants	OG0009

Title

Denominators

Categories

Title	Measurements
	OG0005

Secondary

Overall Response Rate

Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.

As specified in the protocol, only participants treated at the MTD are included in this outcome measure.

Posted

Number

95% Confidence Interval

percentage of Participants with Response

Up to 12 months

ID	Title	Description
OG000	Participants Treated at MTD	Participants treated at MTD.

Units	Counts
Participants	OG00013

Secondary

Progression Free Survival

Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.

As specified in the protocol, only participants treated at the MTD are included in this outcome measure.

Posted

Median

95% Confidence Interval

Months

Up to 12 months

ID	Title	Description
OG000	Participants Treated at MTD	Participants treated at MTD

Units	Counts
Participants	OG00013

Secondary

Overall Survival

Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date

As specified in the protocol, only participants treated at the MTD are included in this outcome measure.

Posted

Median

95% Confidence Interval

Months

Up to 12 months

ID	Title	Description
OG000	Participants Treated at MTD	Participants treated at MTD

Units	Counts
Participants	OG00013

Secondary

Hematologic Response

Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML

As specified in the protocol, only participants treated at the MTD are included in this outcome measure.

Posted

Number

Number of Participants achieving CR

Up to 12 months

ID	Title	Description
OG000	Participants Treated at MTD - sAML	Participants Treated at MTD - sAML
OG001	Participants Treated at MTD - MDS	Participants Treated at MTD - MDS

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1 Dose Level 1	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy	3	3	2	3	3	3
EG001	Phase 1 Dose Level 2	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10^7 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy	3	3	0	3	3	3
EG002	Phase 1 Dose Level 3	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10^7 CD4 T Cells/kg CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy	2	3	3	3	3	3
EG003	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at MTD. CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes: Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent Standard of Care Chemotherapy: Standard of care cytarabine-based chemotherapy	5	10	1	10	10	10

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Fever	General disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG0030 events0 affected10 at risk
Lung Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Skin Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Delirium	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG0030 events0 affected10 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG0021 events1 affected3 at risk EG003
Left ventricular systolic dysfunction	Cardiac disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Ascites	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events1 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Fever	General disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Endocarditis infective	Infections and infestations	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Lung infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected3 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0002 events2 affected3 at risk EG0013 events3 affected3 at risk EG0022 events2 affected3 at risk EG003
Skin infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Vascular access complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Blood bilirubin increased	Investigations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Platelet count decreased	Investigations	Systematic Assessment	EG0004 events2 affected3 at risk EG0013 events1 affected3 at risk EG0022 events1 affected3 at risk EG003
White blood cell decreased	Investigations	Systematic Assessment	EG0004 events3 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0006 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Delirium	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases