Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

CART123 cells; cyclophosphamide; fludarabine

CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with a split dosing approach of CART123 cells (10% Day 0; 30% Day 1; 60% Day 2) for Cohort 1a/1b or a single IV administration of CART123 cells for Cohort 2.

The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose, preceded by lymphodepleting chemotherapy, is 1-2x10\^6 CART123 cells/kg for Cohort 1a, 5x10\^6 CART123 cells/kg for Cohort 1b, or 2x10\^6 CART-123 cells/kg for Cohort 2. The protocol-specified minimum acceptable dose for infusion is 1x10\^5 CART123 cells/kg.

EmergingMed

Care Box Health

Saar Gill, MD, PhD

Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in Acute Myeloid Leukemia (AML) subjects.

This is a Phase 1 study to determine the safety, feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with a split dosing approach of CART123 cells (10% Day 0; 30% Day 1; 60% Day 2) for Cohort 1a/1b or a single IV administration of CART123 cells for Cohort 2.

The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose, preceded by lymphodepleting chemotherapy, is 1-2x10\^6 CART123 cells/kg for Cohort 1a, 5x10\^6 CART123 cells/kg for Cohort 1b, or 2x10\^6 CART-123 cells/kg for Cohort 2. The protocol-specified minimum acceptable dose for infusion is 1x10\^5 CART123 cells/kg for all cohorts.

It is recommended per routine clinical care, that all subjects with marrow aplasia at Day 28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study, however subjects will continue to be followed on study. All subjects should therefore have a previously identified stem cell donor in order to participate in this study. Please see Section 6.8 for additional details.

All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion (Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.

Lentivirally Redirected CD123 Autologous T Cells in AML

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Refractory or Relapsed Acute Myeloid Leukemia

Assess the safety of CART123 cells in AML subjects following lymphodepletion with cyclophosphamide + fludarabine.

Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.

Estimate the efficacy of at least 1 dose of CART123 cells in AML subjects

Overall survival (OS) and progression-free survival (PFS)

Need for rescue allogeneic hematopoietic cell transplantation (alloHCT)

University of Pennsylvania

CART123 cells following lymphodepleting chemotherapy in pediatric patients with relapsed/refractory AML. Subjects will be treated with a single IV dose of CART123 cells on Day 0.

Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).

This is a Phase 1 study to determine the safety, manufacturing feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in pediatric subjects with relapsed/refractory AML.

Subjects will receive CART123 cells via a single IV infusion at a dose of 2x10\^6 CART123 cells/kg, following lymphodepleting chemotherapy. The total dose administered to each subject will be based on the subject's body weight obtained at the time of apheresis. The minimum acceptable dose for infusion is 1x10\^5 CART123 cells/kg.

There will be a 28-day stagger between the first 3 subject infusions, such that the next subject may not receive treatment (lymphodepleting chemotherapy plus CART123 cells) until the previous subject has completed their Day 28 safety follow-up visit and a DLT assessment has been performed. Subsequent infusions will be staggered by a minimum of 14 days.

It is recommended that subjects with marrow aplasia at Day 28+/-5 undergo an allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study; however, subjects will continue to be followed onstudy. All subjects must, therefore, have a previously identified stem cell donor as part of their eligibility to participate in this study.

All subjects will be followed monthly for up to 6 months after the CART123 cell infusion (Day 0). Thereafter, subjects will be transitioned into LTFU for up to 15 years post infusion.

CD123 Redirected T Cells for AML in Pediatric Subjects

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Pediatric Subjects With Refractory or Relapsed Acute Myeloid Leukemia

The duration of in vivo survival of CART123 cells ("persistence") is defined as the period of time above the limit of detection of Q-PCR for peripheral blood CART123 transgene sequences and/or flow cytometry for scFv surface expression.

Occurrence of adverse events that are possibly, probably, or definitely related to CART123 cells

Percentage of manufacturing products that meet release criteria

Overall Response Rate (ORR) at 28 +/- 5 days

1. Standard morphologic complete response criteria (malignant blasts \< 5% with count recovery)
2. Malignant blasts \< 5% without count recovery, and
3. Minimal residual disease assessment

Change of blast count in the peripheral blood and marrow using standard clinical criteria (CBC with differential count, marrow aspirate with differential count) and flow cytometry

Progression-free survival (PFS) for all subjects; PFS will be followed until the time of first relapse or receipt of additional therapy, excluding alloHCT for marrow aplasia.

Time between date of when the response criteria of CR/CRi was met to the date of relapse

Percentage of subjects proceeding to alloHCT (or second allogeneic HCT)

Ceramide NanoLiposome will be administered by Intravenous Dosing twice per week in accordance with the protocol relative to dose escalation. There is no placebo group or arm of the study.

Ceramide NanoLiposome will be given by IV twice a week. The dose, which is based on body size, will be increased for the next group of patients if the first group of patients tolerates that dose and it will decrease for the next group if they do not tolerate the dose.

Ceramide NanoLiposome (Ceraxa)

James H Adair, Ph.D.

Bernadette M Adair, BS

Wanda Neidig

Racheal Griffith, RN

David Claxton, MD

Cory Caldwell

Jungeun Kim

Michael Keng, MD

Daniel Vlock, MD

Christopher Prior, Ph.D.

The study explores whether Ceramide NanoLiposome (CNL) combined with other conventional cancer-fighting drugs makes them work better.

The research team has shown that C6 ceramide nanoliposome (CNL) has anti-cancer activity in laboratory models of AML and that when it is combined with other cancer-fighting drugs, it works better.

The primary goal of this study is to evaluate the safety of CNL given without other cancer treatments in patients with AML where either their initial treatment didn't work or it stopped working and your AML came back (refractory or relapsed AML, or RR-AML). This study seeks to determine the right dose to start with in later studies when CNL is combined with other drugs.

CNL is given by intravenous (IV) infusion and will be given twice a week in this study. Participants will receive study treatment as long as it is considered safe for them to continue, though their disease status will be checked regularly to make sure that their disease has not gotten worse. Blood samples will be collected at many time-points in order to see how their bodies are responding to the drug and how long it stays in the blood.

The first patients in the study will start at one dose of the drug and, if that is shown to be safe, the next group will be treated at a slightly higher dose. Participants will be given CNL by intravenous (IV) infusion twice a week over about 2 hours and then they will be monitored for about 2 hours to make sure they don't have any bad side effects, but initially patients will be required to stay at the site for about 6 hours after the start of the infusion in order to get blood draws to see how long the drug stays active in their system.

Participants will have a bone marrow biopsy before their second "cycle" of drug (after about 1 month) and then again before their third cycle of drug in order to see how their disease is responding. After that, bone marrow biopsies will be about every other cycle based on what the study doctor recommends. If the doctor doesn't think that CNL is helping their disease, of if their doctor decides that it is not safe for them to continue, they will be taken off study treatment. Participants will be followed for safety and disease status for up to 6 months.

Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Phase I Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (RR-AML)

Dose Limiting Toxicities within the first cycle of CNL monotherapy. See section 13.5 of Protocol for the complete list of Dose Limiting Toxicities

Severity of Adverse Event As Described in Protocol

Duration of Adverse Events, As Described in Protocol, measured in days

Duration of therapy provided as measured in days

Dose levels administered in milligrams per m2

Maximum Serum Concentration measured, in nanograms/milliliter

Time to maximum concentration measured, in minutes

Time for drug to be reduced to half of the starting concentration (in minutes)

The Amount of Study Drug Cleared per unit time (Nanograms/Minute)

Ratio of Ceramide 16 to Ceramide 24 (ng of C16/ng of C18) from bone marrow biopsy

Complete Response with Incomplete Hematological Recovery as defined by blasts in bone marrow

Partial Remission (as defined by blasts in bone marrow)

Grade 3 and 4 adverse events as defined by CTCAE v5.0

Overall response of CNL monotherapy in patients with RR-AML: Complete remission (CR) + Complete remission with incomplete count recovery (CRi) + partial response (PR). CR, CRi and PR as defined as European LeukemiaNet 2017 (ELN 2017) response criteria

Event-free survival (EFS): the time from registration until documented refractory disease, relapse after achieving CR/CRi, or death from any cause, whichever is observed first

Quality of life according to EORTC Quality of Life Questionnaire C30

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lentivirally Redirected CD123 Autologous T Cells in AML	NCT03766126	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	18 Years -	University of Pennsylvania
CD123 Redirected T Cells for AML in Pediatric Subjects	NCT04678336	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	1 Year - 29 Years	University of Pennsylvania
CD123 Redirected T Cells for AML in Pediatric Subjects	NCT04678336	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L...	CART123 cells; ...	1 Year - 29 Years	University of Pennsylvania
Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia	NCT04716452	Acute Myeloid L... Acute Myeloid L...	Ceramide NanoLi...	18 Years -	Keystone Nano, Inc

Spots Global Cancer Trial Database for acute myeloid leukemia, refractory