Neoplasms

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All Conditions

Immune System Diseases

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Rare Diseases

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Leukemia, Lymphoid

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Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

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Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

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Leukemia, B-Cell

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B-cell Lymphoma

Chronic Graft Versus Host Disease

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Antineoplastic Agents

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All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Dimethoate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

1.5 x 10\^6 transduced T cells/kg (± 20%)

500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3

Cyclophosphamide injection

30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3

Fludarabine Injection

Cells are to be infused intravenously (IV) over 30 minutes or less via nonfiltered tubing either by gravity or a peristaltic pump, gently agitating the bag during infusion to prevent cell clumping

CD19-CD34t metabolically programmed CAR transduced T-cells

Alan Brisendine

Jasmin Brooks

Alan Brisendine, CCRP

Brian Hess, MD

Brian Hess, PHD

This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Although CD19 CAR T-cell therapy is a dynamic scientific and clinical breakthrough for CD19+ NHL, issues still remain in terms of relapse, toxicity, and availability. This trial will incorporate a CD34 tag (CD34t) into the CAR T-cell construct, thus allowing a more purified CAR T-cell product via CD34 selection. This purification step will hopefully lead to an improvement in safety/toxicity. Furthermore, the issue of CD19 CAR T-cell relapse has been linked to a lack of CAR T-cell fitness. With the knowledge that Th1 T-cell subsets have improved effector function and Th17 T-cell subsets have improved persistence, the investigators plan to expose the collected T-cells to priming conditions that lead to a metabolically enhanced CAR-T cell product akin to a Th1/17 hybrid cell. The investigators hypothesize that these metabolically programmed CD19 CAR-T cells will yield a high- quality product with enhanced persistence and anti-tumor efficacy when purified based on CD34t expression.

Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL

A Phase 1b Dose Escalation Study of Metabolically Fit CD19 Chimeric Antigen Receptor (CAR) T Cells With CD34 Selection Markers in Adult Patients With Relapsed or Refractory CD19 B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Maximum tolerated dose (MTD), maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of CD19-CD34t metabolically programmed CAR T-cells

Rate of grade 3 or higher cytokine release syndrome(CRS)

rate of grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)

1. Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on overall response rate (ORR) and complete remission (CR) rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL based on progression free survival (PFS), duration of response (DOR), and overall survival (OS)

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on ORR and CR rate. The response rate for patients with NHL will be determined by the 2014 Lugano IWG criteria. The response rate for CLL/SLL patients will be determined by the 2018 iwCLL criteria

Anti-tumor activity of CD19-CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell NHL or CLL/SLL treated at the RP2D based on PFS, DOR and OS.

Safety of CD19-CD34t metabolically programmed CAR T-cells at the RP2D, including all grade incidence of CRS and ICANS

Medical University of South Carolina

Assistant Professor

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Leukemia, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

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Anti-Inflammatory Agents

Antiemetics

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Anti-Infective Agents

Dexamethasone

Melphalan

Lenograstim

Lenalidomide

Bortezomib

Dexamethasone acetate

Ixazomib

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Fludarabine+Melphalan followed by Allogeneic SCT.

Consolidated Chemotherapy for Patients Unable to Receive Transplantation

Allogeneic Stem Cell Transplant: Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients.

Allogeneic Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation :Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day followed collecting CD34+ peripheral blood stem cells . Day 0 Infusion of autologous stem cells. Patients during 3-6 months after the 1st SCT will undergo a 2nd SCT. Patients who had not enough PBSC will undergo a 1st SCT.

Autologous Hematopoietic Stem Cell Transplantation x 1 or x 2

conditioning regimen: autologous ARM: Day -2 Melphalan 200 mg/m\^2/day IV over 30 minutes. allogeneic ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes

Melphalan Given IV

conditioning regimen:Days -6,-5,-4,-3 Fludarabine 30 mg/m\^2/day IV

Bortezomib and dexamethasone(VD),Ixazomib and dexamethasone(ID)

PI and dexamethasone as maintenance therapy

Oral lenalidomide at the starting dose of 25mg on days 1-21 every 28 days or days 1-14 every 21 days. Dexamethasone at 20mg twice weekly on days 1,2,4,5,8,9,11\&12 of each 21-day.

PI+IMids+Dexamethasone as Consolidated Chemotherapy

WEI W SUI, Dr.

GANG AN, Dr.

WEI W SUI, Master

Lu G Qiu, Dr.

The clinical trial was conducted in a cohort of young, high-risk myeloma patients who were designed to receive a combination of high-dose chemotherapy with allogeneic or autologous hematopoietic stem cell transplantation. The objective was to assess the progression free survival (PFS), overall survival (OS),and overall response rate (ORR) of the overall treatment.

50 cases of HR-NDMM patients were divided into two groups nonrandomizedly. TE group received hematopoietic stem cell transplantation after induction therapy. Allo-sct for the young patients with suitable donors, Asct for the others. TNE group received consolidation therapy after induction therapy. All patients received PI-based maintenance therapy.

a Clinical Trial of Efficacy and Safety of the Holistic Treatment of Young High-risk Multiple Myeloma Patients

Phase II Open Lable Clinical Study Efficacy and Safety of the Holistic Treatment for Young Patients With High-Risk Multiple Myeloma

PFS is defined as the duration from the data of registration to either progressive disease or death, whichever comes first.

ORR is defined as the proportion of subjects who achieve PR to better rate, according to the IMWG criteria

OS is defined as the duration from the data of registration to death.If the subject is alive, the data will be censored as being alive; the vital status is unknown as last known.

aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999).

GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death cGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.

Number of patients with non-relapse mortalities

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL	NCT05702853	B-cell Non Hodg... Chronic Lymphoc...	Cyclophosphamid... Fludarabine Inj... CD19-CD34t meta...	18 Years -	Medical University of South Carolina
a Clinical Trial of Efficacy and Safety of the Holistic Treatment of Young High-risk Multiple Myeloma Patients	NCT04008888	Multiple Myelom... Plasma Cell Leu... Extramedullary ... Loss of Chromos... t(14;16) t(4;14) T(14;20) 1Q21 Amplificat... Complex Karyoty...	Allogeneic Hema... Autologous Hema... Melphalan Given... Fludarabine Inj... PI and dexameth... PI+IMids+Dexame...	18 Years - 60 Years	Institute of Hematology & Blood Diseases Hospital, China

Spots Global Cancer Trial Database for fludarabine injection