Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Antibodies

Vaccines

Cetuximab

Immunomodulating Agents

Immunoglobulins

Liver Extracts

Antineoplastic Agents, Immunological

The treatment schedule includes: (1) the priming step with two ID AlloStim® injections (Days 0 and 3), an additional two ID injections followed by IV infusion of AlloStim® (Days 7 and 10); (2) the vaccination step with cryoablation of a single metastatic lesion followed by injection of AlloStim® into the ablated tumor and IV infusion of AlloStim® on protocol day 14, followed by IV infusion of AlloStim® on Day 17 (3) the activation step with an IV study drug infusion on Day 21 and (4) the booster step with IV booster infusions of AlloStim® on days 49 and 77. Additional booster infusions can be administered monthly at the discretion of the Investigator.

All subjects will be assigned Physician's Choice (PC) therapy. PC can consist of best supportive care (BSC) or any US-FDA-approved cancer drug (e.g. Cetuximab) administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated.

AlloStim® is derived from the blood of normal blood donors and is intentionally mismatched to the recipient. CD4+ T-cells are separated from the blood and differentiated and expanded for 9-days in culture to make an intermediary called T-Stim. AlloStim is made by incubating T-Stim cells for 4h with antibody coated microbeads. The cells with the beads still attached are suspended in infusion media and loaded into syringes. The syringes are shipped refrigerated to the point-of-care.

AlloStim®

percutaneous ablation of a single metastatic tumor lesion usually in liver. The procedure is conducted under CT or ultrasound image-guidance.

cryoablation

Physician's Choice therapy can consist of best supportive care (BSC) or any US-FDA approved cancer drug (e.g. Cetuximab) administrated as a monotherapy at the manufacturer's recommended dose. The treatment schedule shall be prospectively determined and administered as tolerated

Physician's Choice (PC)

Wirote Lausoontornsiri, MD

Thu Bui, BS

This is a personalized anti-cancer vaccine protocol which includes an in-situ (in the body) cancer vaccine step which combines killing a single metastatic tumor lesion by use of cryoablation in order to cause the release of tumor-specific markers to the immune system and then injecting bioengineered allogeneic immune cells (AlloStim) into the lesion as an adjuvant in order to modulate the immune response and educate the immune system to kill other tumor cells where ever they reside in the body.

Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Metastasis is the main reason of death in CRC patients. The current drugs used to treat colorectal cancer provide important treatment options for patients, their limitations including drug resistance, poor efficacy and severe side effects. Development of new therapeutic strategies for KRAS mutant as well as BRAF mutant tumors are therefore highly needed in order to offer a new category of drug (immunotherapy). This study targets the population of mCRC patients that have progressed after two lines of chemotherapy and are not eligible for targeted therapies due to a mutation in KRAS or BRAF.

This is a Phase II/III, randomized, open-label, multicenter, controlled, two arm study designed to determine the efficacy in terms of OS and the safety of the InSituVax (AlloStim+ Cryoablation) personalized in-situ anti-cancer vaccine protocol (Treatment Arm) compared with Physician's Choice (PC) of Treatment + Cryoablation (Control Arm) in Metastatic Colorectal Cancer. Subjects are randomized 2:1 into the treatment or control arms.

AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer

A Phase II/III, Randomized, Open Label, Controlled, Two Arm Study Comparing Overall Survival of AlloStim® Combined With Cryoablation to a Physician's Choice Combined With Cryoablation in 3rd Line Treatment for Metastatic Colorectal Cancer

blood samples will be evaluated for immunological response and a determination made as to whether immunological response correlates with survival

To document the longitudinal changes in tumor burden by Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Related Response Criteria (irRC)

To assess whether cryoablation combined with AlloStim treatment (arm 1) provides an overall survival (OS) advantage when compared to treatment with cryoablation combined with physician's choice (arm 2).

Safety will be evaluated by physical exam, changes in laboratory values and patient reported symptoms

To assess change in HRQoL between treatment arms

Immunovative Therapies, Ltd.

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

This is a rollover protocol designed to provide long-term follow-up to all subjects previously enrolled in Adicet Bio allogeneic γδ CAR T cell study.

Patients will be followed for up to 15 years post treatment of Adicet Bio allogeneic γδ CAR T cell investigational products.

No study drug is administered in this study. Patients who have received Adicet allogeneic γδ CAR T cell therapy will be evaluated in this trial for long-term safety and efficacy

ADI-001

The purpose of this study is to assess long-term side effects from subjects who receive an Adicet Bio γδ CAR T cell product. Subjects will join this study once they complete the parent interventional study. No additional study drug will be given, but subjects can receive other therapies for their cancer while they are being followed for long term safety in this study. For a period of 15 years from the first administration of Adicet Bio allogeneic γδ CAR T cell product, subjects will be assessed for long-term safety and survival through collection of data that include safety, efficacy, pharmacokinetics and immunogenicity.

This is a non-therapeutic, multi-center, long-term follow-up (LTFU) study of subjects who received an Adicet Bio allogeneic γδ CAR T cell product that has been genetically engineered to express the anti-CD20 CAR by transduction with a self-inactivating, replication incompetent gamma retroviral vector. The period of follow-up is 15 years after the administration of the γδ CAR T cell product.

The study involves up to 15 years post-infusion monitoring of subjects who have been exposed to a genetically engineered CAR in Adicet Bio clinical studies. Upon early termination/discontinuation or completion of the parent interventional study, subjects will enroll into this study. Collection of these data will further define the risk-benefit and efficacy profile Adicet allogeneic γδ CAR T cell investigational products.

This is an observational study, and the elements of the study design are per published guidelines for gene therapy medicinal products that utilize integrating viral vectors such as gamma retrovirus and it is important to evaluate any delayed adverse events after infusion with such products.

Test for RCR following treatment with Adicet Bio allogeneic CAR T cell products. Also will continue to follow immunogenicity assessments of Adicet Bio allogeneic CAR T cell products by using patients blood specimens to assess humoral as well as cellular responses to CAR T cell products. Persistence of ADI-001 will be measured in blood.

Long-term Follow-up Study of Allogeneic Gamma Delta (γδ) CAR T Cells

Long-term Follow-up Protocol for Subjects Treated With Adicet Allogeneic Gamma Delta (γδ) CAR T Cell Investigational Products

Occurrence of new Adverse Events of Special interests, Serious AEs and malignancies

Test for RCR following treatment with Adicet Bio allogeneic γδ CAR T cell products by QCR analysis

Defined as duration from dosing to undetectable levels of Adicet allogeneic γδ CAR T cell per microliter blood

Progression Free Survival by Lugano Criteria

Overall Survival from date of first treatment until date of death

Adicet Bio, Inc

Heart and Blood Diseases

Symptoms and General Pathology

Leukemia

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Intravenous AlloStim infusion on day 1 and day 7

Intravenous AlloStim infusion on day 1, day 7 and day 14

Intravenous AlloStim infusion on day 1, day 7, day 14 and day 21

single intravenous infusion of 1 x 10\^9 AlloStim cells

AlloStim

Intravenous infusion of 1 x 10\^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10\^8 AlloStim on day 7

Intravenous infusion of 1 x 10\^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10\^8 AlloStim on day 7 and day 14

Intravenous infusion of 1 x 10\^9 AlloStim on day 1 and a second intravenous infusion of 1 x 10\^8 AlloStim on day 7, day 14 and day 21

Dr. Michael Har-Noy

The purpose of this study is to determine the safety and anti-tumor effects of an experimental immunotherapy drug, called AlloStim, which is intentionally mis-matched immune cells which are designed to elicit the same anti-tumor mechanism that occurs in allogeneic bone marrow/stem cell mini-transplant (BMT) procedures, without the toxicity associated with graft vs. host disease (GVHD).

AlloStim is combination biological drug and medical device formulation consisting of allogeneic immune cells that have been expanded and differentiated ex-vivo. These cells are conjugated to monoclonal antibody coated microparticles prior to infusion. The immune cells are living CD4+ memory Th1-like T-cells (T-Stim) that are differentiated from precursors purified from normal donor blood. AlloStim is a composition of T-Stim cells conjugated to paramagnetic epoxy covered microparticles (4.5micron) with covalently bound anti-CD3/anti-CD28 monoclonal antibodies (Dynabeads® ClinExVivo™ CD3/CD28) at a 2:1 bead:cell ratio. The T-Stim cells are intentionally mismatched to the recipient.

The graft vs. tumor (GVT) effect that occurs after allogeneic bone marrow transplant (BMT) is a curative therapy for advanced hematological malignancy but the clinical application of GVT is severely limited by graft vs. host disease (GVHD) toxicity. AlloStim is designed to elicit the "mirror" of the GVT/GVHD effects in the host immune system. Rather than trying to separate these effects, we have proposed that the effects could remain associated and "mirrored" onto the host immune system creating linked host vs. tumor (HVT) and host vs. graft (HVG) effects. We hypothesized that allogeneic Th1 memory cells activated at time of infusion to produce type 1 cytokines and express CD40L would elicit HVT/HVG "mirror effects" in immunocompetent cancer patients.

A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy

A Phase I/II Study of Intentionally Mis-Matched, Allogeneic Th1 Memory Cells (AlloStim) Conjugated With CD3/CD28-coated Microbeads in Patients With Relapsed or Refractory Hematological Malignancy

Hadassah Medical Organization

Leukemia, Myeloid, Acute

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Antirheumatic Agents

Antibodies, Monoclonal

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Daratumumab

Elotuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

FT538 monotherapy in subjects with r/r AML

FT538 in combination with daratumumab in subjects with r/r MM

FT538 in combination with elotuzumab in subjects with r/r MM

Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell

FT538

Fate Trial Disclosure

This is a Phase I dose-finding study of FT538 as monotherapy in acute myeloid leukemia (AML) and in combination with monoclonal antibodies in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

FT538 in Subjects With Advanced Hematologic Malignancies

A Phase I, Open-Label, Multicenter Study of FT538 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination With Monoclonal Antibodies in Relapsed/Refractory Multiple Myeloma

Proportion of subjects who achieve a CR, CRMRD-, CRi, MLFS, or PR, as determined by the investigator according to 2017 ELN criteria for AML, and the proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG for MM response criteria

Defined as the duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death due to progressive disease, as determined by the investigator according to standard IMWG response criteria

Defined as the time from first dose of study treatment to disease progression or relapse, or to the day of death from any cause, as determined by the investigator according to standard IMWG response criteria

Defined as the time from initial CR (including CRMRD-, CR, and CRi) to hematologic relapse or death due to any cause, as determined by the investigator according to 2017 ELN criteria for AML, and defined as the duration from the start of sCR or CR until the time of relapse from sCR or CR, as determined by the investigator according to standard IMWG response criteria for MM

defined as the time from first dose of lympho-conditioning to the date of PD, or relapse from CR or CRi, or death from any cause, according to 2017 ELN criteria

defined as the time from first dose of lympho-conditioning to death from any cause

defined as the time from first dose of lympho-conditioning to best response

The PK of FT538 in peripheral blood will be reported as the relative percentage of product (FT538) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points

Fate Therapeutics

ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).

ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Adicet Medical Director

David Miklos, MD

Jay Spiegel, MD

Asad Bashey, MD

Umar Farooq, MD

Don A Stevens, MD

Matthew Cortese, MD

Houston Holmes, MD

Sattva Neelapu, MD

Krish Patel, MD

This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.

ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:

Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.

Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.

The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.

A Phase 1 Study of ADI-001 in B Cell Malignancies

A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T Cells in Adults With B Cell Malignancies

This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).

This primary endpoint will be used to determine the MTD/MAD of ADI-001

Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Alemtuzumab

ALLO-501A is an allogeneic CAR T cell therapy targeting CD19

ALLO-501A

ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen

ALLO-647

Allogene Therapeutics Inc.

Yasmin Adam

Tiffany Tran

Geoffrey Shouse, MD

Christopher Hannigan

Linnea Nichols

Ben Burtness

Rushang Patel, MD

Rebecca Delph

Caitlin Guzowski

Kelly Jenkins

Rachel Martino

Ashley Spalding

Grace Bae

Olalekan Oluwole, MD

Tiffany Cardona

Christine Terraciano

Swapna Binoy

This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2)

A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501A, an Anti-CD19 Allogeneic CAR T Cell Therapy, and ALLO-647, an Anti-CD52 Monoclonal Antibody, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma (LBCL)

Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion

DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion

ORR defined as assessment of CR and PR using Lugano classification criteria 2014

DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression or death, whichever comes first per (Cheson et al, 2014)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer	NCT01741038	Metastatic Colo...	AlloStim® cryoablation Physician's Cho...	18 Years -	Immunovative Therapies, Ltd.
Long-term Follow-up Study of Allogeneic Gamma Delta (γδ) CAR T Cells	NCT04911478	Lymphoma, Folli... Lymphoma, Mantl... Marginal Zone L... Primary Mediast... Diffuse Large B... Lymphoma, Non-H...	ADI-001	18 Years -	Adicet Bio, Inc
A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy	NCT00558675	Hematological M... Leukemia Lymphoma Multiple Myelom...	AlloStim AlloStim AlloStim AlloStim	18 Years -	Immunovative Therapies, Ltd.
FT538 in Subjects With Advanced Hematologic Malignancies	NCT04614636	Acute Myeloid L... AML, Adult Multiple Myelom... Myeloma	FT538 Cyclophosphamid... Fludarabine Daratumumab Elotuzumab	18 Years -	Fate Therapeutics
A Phase 1 Study of ADI-001 in B Cell Malignancies	NCT04735471	Lymphoma, Folli... Lymphoma, Mantl... Marginal Zone L... Primary Mediast... Diffuse Large B... Lymphoma, Non-H...	ADI-001 Fludarabine Cyclophosphamid...	18 Years -	Adicet Bio, Inc
Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2)	NCT04416984	Relapsed or Ref...	ALLO-501A ALLO-647 Fludarabine Cyclophosphamid...	18 Years -	Allogene Therapeutics
A Phase I/II Study of Mis-Matched Immune Cells (AlloStim) in Patients With Advanced Hematological Malignancy	NCT00558675	Hematological M... Leukemia Lymphoma Multiple Myelom...	AlloStim AlloStim AlloStim AlloStim	18 Years -	Immunovative Therapies, Ltd.
FT538 in Subjects With Advanced Hematologic Malignancies	NCT04614636	Acute Myeloid L... AML, Adult Multiple Myelom... Myeloma	FT538 Cyclophosphamid... Fludarabine Daratumumab Elotuzumab	18 Years -	Fate Therapeutics

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