Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Hematologic Neoplasms

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Gemcitabine

Oxaliplatin

Bendamustine Hydrochloride

Rituximab

Polatuzumab vedotin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoconjugates

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

Antineoplastic Agents, Alkylating

Alkylating Agents

Single infusion of 2.5 × 10\^6 CAR-transduced autologous T cells per kg/body weight.

Immunochemotherapy will be administered from the following 2 predefined regimens: R-GemOx (8 cycles of 14 days each) or BR plus polatuzumab vedotin (6 cycles of 21 days each). BR plus polatuzumab vedotin will be capped at a maximum of 10% of participants; i.e. a maximum of 8 participants will be randomised to the BR plus polatuzumab vedotin regimen.

Participants from the SoC arm are allowed to be treated with CAR T-cell MB-CART2019.1 upon request by the investigator if at least one of the following criteria is confirmed by the IRC:

* Relapse or progression occurring at any time within 1 year after randomisation.
* Failure to achieve PR or CR at or beyond Week 8 after randomisation (after 4 cycles of R-GemOx or 3 cycles of BR plus polatuzumab vedotin) and the start of a new anti-lymphoma therapy is warranted.

MB-CART2019.1 is designed to effectively target malignant B cells in patients suffering from late stage haematological B-cell malignancies. MB-CART2019.1 consists of autologous cluster of differentiation CD20/CD19 chimeric antigen receptor (CAR) transduced CD4/CD8 enriched T cells, derived from a leukapheresis and processed by using the CliniMACS Prodigy® device.

MB-CART2019.1

Immunochemotherapy will be administered as per arm description.

R-GemOx or BR plus polatuzumab vedotin

Gregor Zadoyan, Dr.

Silke Holtkamp, Dr.

Hildegard Greinix, Prof.

Jakob Rudzki, Dr.

Veronika Buxhofer-Ausch, Dr.

Richard Greil, Prof.

Ulrich Jaeger, Prof.

Marie Maerevoet, Prof.

Peter Vandenberghe, Prof.

Marc André, Prof.

David Belada, Dr.

Michal Kascak, Dr.

Francois Lemmonier, Dr.

Ibrahim Yakoub-Agha, Prof.

Emmanuel Bachy, Dr.

Didier Philippe Blaise, Dr.

Guillaume Cartron, Prof.

Thomas Gastinne, Dr.

Catherine Thieblemont, Prof

Francois-Xavier Gros, Dr.

Stephanie Guidez, Dr.

Roch Houot, Dr.

Pierre Bories, Dr.

Pierre Feugier, Prof.

Christoph Schmid, Dr.

Peter Borchmann, Prof.

Andreas Mackensen, Prof. Dr.

Bastian Von Tresckow, Dr.

Ahmet Elmaagacli, Dr.

Francis Ayuk, Prof. Dr.

Peter Dreger, Prof. Dr.

Vladan Vucinic, Dr. med.

Veit Bücklein, Dr.

Matthias Stelljes, Prof. Dr.

Matthias Edinger, Prof. Dr.

Wolfgang Bethge, Prof. Dr.

Arpad Illes, Prof. Dr.

Barbara Botto, Dr.

Laimonas Griskevicius, Dr.

Marie Kersten, Dr.

Tom van Meerten, Dr.

Aniko Sijs Szabo, Dr.

Pim Mutsaers, Dr.

Tomasz Wrobel, Prof.

Gloria Iacoboni Garcia-Calvo, Dr.

Valentin Ortiz, Dr.

Anna Sureda Balari, Dr.

Raul Cordoba Mascunano, Dr.

Antonio Salar Silvestre, Dr.

Carlos Grande Garcia, Dr.

Alejandro Martin Garcia-Sancho, Dr.

Virginia Escamilla Gomez, Dr.

Gunilla Enblad, Dr.

Peter Borchmann, Prof. Dr.

This is a pivotal Phase II randomised, multi-centre, open-label study to evaluate the efficacy and safety of MB-CART2019.1 compared to standard of care therapy in participants with relapsed/refractory diffuse large B-cell lymphoma, who are not eligible for high-dose chemotherapy and autologous stem cell transplantation.

This study should determine superiority of MB-CART2019.1 treatment compared to SoC therapy with R-GemOx (rituximab, gemcitabine and oxaliplatin) with respect to event-free survival in second-line therapy in participants with R-R DLBCL, who are non-eligible for high-dose chemotherapy and autologous stem cell transplantation.

MB-CART2019.1 is designed to effectively target malignant B cells in patients suffering from late stage haematological B-cell malignancies. MB-CART2019.1 consists of autologous cluster of differentiation CD20/CD19 chimeric antigen receptor (CAR) transduced CD4/CD8 enriched T cells, derived from a leukapheresis and processed by using the CliniMACS Prodigy®. Patients who are suitable for this study will be randomized 1:1 to either MB-CART2019.1 or SoC. Both treatment arms are unblinded.

MB-CART2019.1 arm: Single infusion of fresh formulation of 2.5 × 10\^6 CAR-transduced autologous T cells. IMP is only to be administered after a lymphodepleting chemotherapy with fludarabine and cyclophosphamide. For MB-CART2019.1 production, patients will undergo a leukapheresis.

SoC arm: R-GemOx (8 cycles of 14 days each) or (10% of SoC arm) BR (Bendamustine/Rituximab) + polatuzumab vedotin (6 cycles of 21 days each). Participants from the SoC arm are allowed to be treated with MB-CART2019.1 upon request by the investigator if at least one of the following criteria is confirmed by the IRC:

* Relapse or progression occurring at any time within 1 year after randomisation.
* Failure to achieve PR or CR at or beyond Week 8 after randomisation (after 4 cycles of R-GemOx or 3 cycles of BR plus polatuzumab vedotin) and the start of a new anti-lymphoma therapy is warranted.

The duration of the active part of the study for each individual participant from screening to the end of the 1-year follow-up after infusion of MB-CART2019.1 cells (experimental arm) or the start of SoC therapy (comparator arm) will be approximately 55 weeks. The LTFU in Year 2 after infusion of MB-CART2019.1 cells or the start of treatment in the comparator arm will not be part of the active part of the clinical study and will be reported separately.

unblinded 1:1 randomization into IMP or SoC

Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients

A Pivotal Phase II Randomised, Multi-centre, Open-label Study to Evaluate the Efficacy and Safety of MB-CART2019.1 Compared to SoC Therapy in Participants With r/r DLBCL, Who Are Not Eligible for HDC and ASCT

Event-free survival (EFS), defined as the time between the date of randomisation and the date of objective disease progression, failure to achieve partial response (PR) or complete response (CR) at or beyond Week 8 after randomisation leading to a new anti-lymphoma therapy or death of any cause, whichever occurs first, based on independent review committee (IRC) assessment.

defined as the time between the date of randomisation and the date of objective disease progression or death of any cause, whichever occurs first, based on IRC assessment.

To evaluate the safety and toxicity of MB-CART2019.1 compared to SoC therapy.

ICON plc

Miltenyi Biomedicine GmbH

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Peripheral blood mononuclear cells were isolated, amplified and cultured in vitro, pretreated with FC regimen, and Anti-CD1a CAR-T cells were transfused.

CAR-T Cell Infusion

Wei Sang, M.D., Ph.D.

To evaluate the efficacy and safety of anti-CD1a CAR-T in the treatment of relapsed refractory acute T-lymphoblastic leukemia/lymphoblastic lymphoma.

Acute T-lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is a highly heterogeneous hematological malignancy usually associated with genetic alterations/mutations in transcription factors that are major regulators of hematopoietic stem/progenitor cell homeostasis and T cell development. 70% of patients develop mass with myeloid invasion and other leukemia symptoms.

CD1a, a transfer membrane glycoprotein, is a cell surface antigen present on cortical T-ALL cells. It is present in 40% of T-ALL cases. Specific expression of this antigen has also been observed in developing cortical thymus cells. It was also slightly expressed in langerhans cells, digital dendritic cells, B lymphocytes and gastrointestinal epithelial cells. CD1a4 was not expressed in CD34+ progenitor cells or T cells during ontogeny. This property of CD1a makes it a suitable target antigen whose targeting minimizes the possibility of non-tumor toxicity.

This study intends to treat r/r CD1a+T-ALL/LBL with CD1a CAR-T to observe its safety and efficacy.

Clinical Study of Anti-CD1a CAR-T in the Treatment of R/R Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma

Clinical Study of Anti-CD1a CAR-T in the Treatment of Relapsed Refractory Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma

The time between treatment and observation of disease progression or death from any cause.

The time interval between patient infusion of CAR-T and death from any cause or the end of follow-up.

The time from the start of CAR-T infusion to the occurrence of any event.

Characterization of the level of CAR T cell expansion in subjects over time.

Characteristics of lymphocyte reduction in subjects

The Affiliated Hospital of Xuzhou Medical University

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

IPI-504

Sundar Jagannath, MD

David S. Siegel, MD; Ph.D

Ivan Borrello, MD

Paul Richardson, MD

This is a phase 1 clinical trial to find the safe, maximum tolerated dose of IPI-504 in patients with relapsed and/or relapsed, refractory multiple myeloma. This study will examine how IPI-504 is absorbed, distributed, metabolized, and eliminated by the body. The study will also evaluate potential anti-tumor activity of IPI-504.

IPI-504 is a novel small molecule inhibitor of heat shock protein 90 (Hsp90), an emerging and recently identified target for cancer therapy. Hsp90 is a protein chaperone that plays a central role in regulating protein homeostasis. Hsp90 regulates the stability of key proteins (called "client proteins") and keeps them in the appropriate three dimensional shape so they can perform their cellular functions. In addition, many of the proteins stabilized by Hsp90 are oncoproteins and cell-signaling proteins important in cancer cell proliferation and cancer cell survival. Thus Hsp90, a single molecular target that is a central integrator of multiple pathways important to cancer, is an ideal novel target for oncologic therapy. Selective inhibition of Hsp90 will affect multiple downstream mechanisms to disrupt tumor growth and selectively kill cancer cells. The anti-neoplastic effects of Hsp90 inhibition have been demonstrated both in vitro and in vivo for a variety of different hematologic and solid tumors including multiple myeloma.

Safety Study of IPI-504 in Patients With Relapsed and Relapsed Refractory Multiple Myeloma

A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Relapsed, and Relapsed Refractory Multiple Myeloma

Infinity Pharmaceuticals, Inc.

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Dexamethasone

Doxorubicin

Liposomal doxorubicin

Pomalidomide

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Pomalidomide + Pegylated Liposomal Doxorubicin + Dexamethasone in an open label, dose escalation study

Pomalidomide administered to 3 cohorts of subjects at escalating doses of 2 (cohort 1), 3 (cohort 2) and 4 mg/dose (cohort 3) per orem (PO). Doses are to be administered once-a-day, for the first 21 days, as part of a 28-day treatment cycle, followed by a 7-day rest period.

Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.

PLD will be given at a dose of 5.0 mg/m2 as a 60 minute IV infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle.

Pegylated Liposomal Doxorubicin (PLD)

Dexamethasone will be given at a dose of 40 mg/dose IV. Doses are to be administered on days 1, 4, 8, and 11 of the 28-day cycle.

James R Berenson, MD

The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of a combination of three different drugs, pomalidomide, pegylated liposomal doxorubicin, and dexamethasone when used to treat relapsed (the disease came back) or refractory (the disease did not respond to past treatment) multiple myeloma. Different dosages (amount of study drug) of pomalidomide are first being tested to determine if there are any side effects or risks associated with combining this study drug with the other two listed. Once the optimal dose is decided on, the study will change its focus to determining the effectiveness of the study drug in this combination.

This is a phase 1/2, multicenter, open label and nonrandomized study to evaluate the efficacy and safety of pomalidomide at daily dosages of 2, 3 or 4 mg in combination with intravenous (IV) dexamethasone at 40 mg/dose and Pegylated Liposomal Doxorubicin (PLD) at 5 mg/m2/dose for subjects with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment, and a follow-up period.

Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles. Subjects are to be treated to a maximum response plus 2 additional cycles (no more than 8 cycles will be allowed) or complete 8 cycles of therapy without disease progression.

Pomalidomide, dexamethasone and PLD will be administered on the appropriate cycle days as shown below.

Cohort 1 Pomalidomide\* - 2 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

Cohort 2 Pomalidomide\* - 3 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

Cohort 3 Pomalidomide\* - 4 mg, Dexamethasone\*\* - 40 mg, PLD\*\* - 5 mg/m2

\* PO Days 1-21

\*\* IV Days 1, 4, 8 and 11

In all cohorts, if an unacceptable dose limiting toxicities (DLT) is not seen in any of the 3 subjects during the first cycle of any dose level, dose escalation will continue. All subjects in a cohort must complete a minimum of 28 days or a full cycle, whichever is longer, without a DLT before enrollment to the next cohort can begin. If a DLT is identified in 1 subject at any dose level during the first treatment cycle, an additional 3 subjects will be recruited to this dose level. A maximum of 6 subjects may be enrolled in each cohort. If an unacceptable DLT is observed in 2 subjects at any dose level, no further subjects will be recruited to this dose level. The maximum tolerated dose (MTD) will be declared as the highest dose level at which fewer than 33% of subjects experienced an unacceptable DLT. If pomalidomide at 4 mg is reached and fewer than 33% of subjects experience an unacceptable DLT, 4 mg will be accepted as the putative MTD. Once the MTD is established, further enrollment will continue to expand that dose cohort until the total sample size of 40 subjects is reached for the entire study. During the phase 2 portion of this study, subjects enrolled will have relapsed/refractory MM resistant to lenalidomide as demonstrated by progressive disease while on lenalidomide or that has relapsed within 8 weeks of the last dose of lenalidomide.

Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma

A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma

Phase 1: To establish the MTD of pomalidomide in combination with dexamethasone and pegylated liposomal doxorubicin

Phase 2: To determine efficacy as evidenced by the best overall response rate (CR + VGPR + PR + MR) following treatment with pomalidomide, dexamethasone and pegylated liposomal doxorubicin

Phase 2: To establish the number of patients with adverse events when using the combination of pomalidomide, dexamethasone and pegylated liposomal doxorubicin

Phase 2: Defined as the time from initiation of therapy to progressive disease

Phase 2: Defined as the time from initiation of therapy to progressive disease or death from any cause, which ever occurs first

Phase 2: Defined as the time from the initiation of therapy to the first evidence of a confirmed response (CR, VGPR, PR or MR)

Phase 2: Defined as the time from first response to progressive disease

Phase 2: Defined as the time from initiation of therapy to death from any cause or last follow-up visit

Celgene Corporation

Oncotherapeutics

Amino Acids

Venetoclax

Daratumumab

Ixazomib

Thalidomide

Glycine

HIV Protease Inhibitors

Protease Inhibitors

Immunosuppressive Agents

Neurotransmitter Agents

Patients with CDK activating alteration receive Abemaciclib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with IDH2 activating mutation receive Enasidenib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with the presence of RAF/RAS mutation receive Cobimetinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with presence of FGFR3 activating mutations receive Erdafitinib in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with t(11;14) translocation will be enrolled in arm E1 and randomized to the venetoclax or the IPd control arm. Patients with relapsed Multiple Myeloma will receive Venetoclax, Ixazomib, Pomalidomide and Dexamethasone every cycle. Each cycle is 28 days long.

Patients with Non-Actionable Genetic Abnormality receive Daratumumab in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with Non-Actionable Genetic Abnormality receive Belantamab mafodotin in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with Non-Actionable Genetic Abnormality receive Selinexor in combination with ixazomib, pomalidomide and dexamethasone (IPd)

Patients with relapsed Multiple Myeloma will receive Abemaciclib and Dexamethasone for the first 2 cycles. Abemaciclib, Dexamethasone, Ixazomib and Pomalidomide from cycle 3 forward. Each cycle is 28 days long.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients	NCT04844866	Diffuse Large B...	MB-CART2019.1 R-GemOx or BR p...	18 Years -	Miltenyi Biomedicine GmbH
Clinical Study of Anti-CD1a CAR-T in the Treatment of R/R Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma	NCT05745181	Acute T-lymphob... Acute T-lymphob...	CAR-T Cell Infu...	18 Years - 70 Years	The Affiliated Hospital of Xuzhou Medical University
Safety Study of IPI-504 in Patients With Relapsed and Relapsed Refractory Multiple Myeloma	NCT00113204	Multiple Myelom...	IPI-504	18 Years -	Infinity Pharmaceuticals, Inc.
Safety Study of IPI-504 in Patients With Relapsed and Relapsed Refractory Multiple Myeloma	NCT00113204	Multiple Myelom...	IPI-504	18 Years -	Infinity Pharmaceuticals, Inc.
Clinical Study of Anti-CD1a CAR-T in the Treatment of R/R Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma	NCT05745181	Acute T-lymphob... Acute T-lymphob...	CAR-T Cell Infu...	18 Years - 70 Years	The Affiliated Hospital of Xuzhou Medical University
Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Relapsed/Refractory Multiple Myeloma	NCT01541332	Multiple Myelom...	Pomalidomide Pegylated Lipos... Dexamethasone	18 Years -	Oncotherapeutics
Myeloma-Developing Regimens Using Genomics (MyDRUG)	NCT03732703	Relapsed Refrac...	Abemaciclib, de... Enasidenib, dex... Cobimetinib, de... Erdafitinib, de... Venetoclax, dex... Daratumumab, de... Belantamab mafo... Selinexor, dexa...	18 Years -	Multiple Myeloma Research Consortium
Safety Study of IPI-504 in Patients With Relapsed and Relapsed Refractory Multiple Myeloma	NCT00113204	Multiple Myelom...	IPI-504	18 Years -	Infinity Pharmaceuticals, Inc.
Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients	NCT04844866	Diffuse Large B...	MB-CART2019.1 R-GemOx or BR p...	18 Years -	Miltenyi Biomedicine GmbH

Spots Global Cancer Trial Database for relapsed refractory