Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Hematologic Diseases

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Participants with relapsed or refractory (R/R) Non-Hodgkin's lymphoma (NHL) will receive escalating doses of ABBV-101, until the maximum administered dose (MAD)/Maximum tolerated dose (MTD) is determined, as part of the approximately 60 month study duration.

Participants with R/R CLL will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 60 month study duration.

Participants with R/R non-germinal center B cell (GCB) diffuse large B-cell lymphoma (DLBCL) will receive ABBV-101 at the dose determined in the dose escalation arm, as part of the approximately 60 month study duration.

ABBV-101

ABBVIE CALL CENTER

ABBVIE INC.

Non-Hodgkin's lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of ABBV-101 in adult participants in relapsed or refractory (R/R) non-Hodgkin's lymphomas: third line or later of treatment (3L) + chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large b-cell lymphoma (DLBCL), non-germinal center B cell (GCB) DLBCL, mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), or transformed indolent NHL. Adverse events will be assessed.

ABBV-101 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-101 and a dose expansion phase to determine the change in disease activity in participants with CLL or non-GCB DLBCL. Approximately 128 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide.

In the Dose Escalation phase of the study participants will receive escalating oral doses of ABBV-101, until the MAD/MTD is determined, as part of the approximately 60 month study duration. In the dose expansion phase of the study participants receive oral ABBV-101, as part of the approximately 60 month study duration .

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies

First-in-Human Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of the BTK Degrader, ABBV-101, in Participants With B-cell Malignancies

AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.

Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.

12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.

Maximum observed serum concentration of ABBV-101.

Area under the serum concentration versus time curve (AUC) of ABBV-101.

Number of participants with response of PR or better per disease-specific criteria.

DOR is defined for participants achieving PR or better as the time from the initial response per Investigator review to disease progression or death of any cause, whichever occurs earlier.

AbbVie

Infections

Epstein-Barr Virus Infections

Lymphoproliferative Disorders

Virus Diseases

Communicable Diseases

Lymphatic Diseases

Immunoproliferative Disorders

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Post-transplant Lymphoproliferative Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Hematinics

Gastrointestinal Agents

Rituximab

Immunomodulating Agents

Liver Extracts

Pancrelipase

Pancreatin

Participants who have failed rituximab will receive IV tabelecleucel.

Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.

Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

tabelecleucel

Aditi Mehta, DO

Amandeep Salhotra, MD

Huynh Cao, MD

Neena Kapoor, MD

Herbert Eradat, MD

William Asch, MD

Udeme Ekong, MD

Amer Beitinjaneh, MD, MPH, MSc

Suhag Parikh, MD

Jean Koff, MD

Sonali Chaudhury, MD

Satayaijt Kosuri, MD

Patrick Hagen, MD

Jean Yared, MD

Sarah Nikiforow, MD

Armin Ghobadi, MD

Koen Van Besien, MD

Ran Reshef, MD

Kevin Curran, MD

Michael Kent, MD

Matthew McKinney, MD

Hanna Rabi, MD

Robert Baiocchi, MD, PhD

Nemecek Eneida, MD

Nancy Bunin, MD

Michelle Hudspeth, MD

Bhagirathbhai Dholaria, MD

Luis Pineiro, MD

Tamra Slone, MD

Kris Michael Mahadeo, MD

James Butterworth, MD

Shyam Panicker, MD, MBBS, MRCP, FRACP, FRCPA

Daniel Chambers, MBBS, MRCP, FRACP, MD

Devendra Hiwase, MD

Rachel Conyers, MD, MBBS, FRACP

Duncan Purtill, MD, MBBS, FRACP, FRCPA

Nina Worel, MD

Willems Evelyne, MD

Daan Dierickx, MD

Victor Lewis, MD

Joerg Krueger, MD

Arjun Law, MD

Edouard Forcade, MD

Eolia Brissot, MD

Franck Morschhauser, MD

Benedicte Neven, MD

Sylvain Choquet, MD

Roberto Cairoli, MD

Patrizia Comoli, MD

Simona Sica, MD

Franco Locatelli, MD

Giaccone Luisa, MD

Eva González-Barca, MD

Lucrecia Yanez, MD

Pere Barba, MD

Gillen Oarbeascoa, MD

Jose Perez-Simon, MD

Juan Montoro, MD

Sridhar Chaganti, MD

Daniele Avenoso, MD

Eduardo Olavarria, MD

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

Study procedures and product administration will be the same for each cohort. Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, participants will receive intravenous tabelecleucel at a dose of 2×10\^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non protocol therapy, or failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy

Atara Biotherapeutics

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Venetoclax

Azacitidine

Antimetabolites

Enzyme Inhibitors

Participants in this group will begin Venetoclax and Azacitidine (VEN/AZA) combination therapy between day +42 and day +100 following hematopoietic cell transplant (HCT) infusion. VEN/AZA combination therapy will be administered for up to six (6) cycles, followed by up to six (6) additional cycles of Venetoclax monotherapy in the absence of disease progression or unacceptable toxicity. Each cycle is 28 days.

Participants may also receive donor lymphocyte infusions (DLI) at the discretion of the treating physician, if certain criteria are met.

Participants will receive up to one year (12 cycles) of study therapy, followed by up to one year of follow-up. Total participation duration is up to two years.

Participants in this group will receive VEN/AZA therapy at the most appropriate dose determined in Part 1. Participants may also receive donor lymphocyte infusions (DLI) at the discretion of the treating physician, if certain criteria are met.

Participants will receive up to one year (12 cycles) of study therapy, followed by up to one year of follow-up. Total participation duration is up to two years.

Venetoclax will be given orally (PO) at the assigned doses of 50 or 100 mg once daily for 7, 14 or 21 days starting at day 1 of each 28-day cycle, for up to 12 cycles.

Azacitidine will be administered at a dose of 20mg/m\^2 once daily subcutaneously (SC) or intravenously (IV) for five days (Days 1-5) of each 28-day cycle.

Donor lymphocyte infusions (DLI) may be administered at the discretion of the treating physician, if certain criteria are met. Participants may receive up to three (3) infusions of donor lymphocytes (a type of white blood cell) at the following dose levels and study timepoints:

* DLI 1: 1x10\^6 cluster of differentiation 3+ (CD3+) cells/kg, after cycle 3
* DLI 2: 5x10\^6 CD3+ cells/kg, after cycle 5, if there is persistent MRD
* DLI 3: 1x10\^7 CD3+ cells/kg, after cycle 7, if there is persistent MRD.

Donor Lymphocyte Infusion

Antonio M Jimenez Jimenez, MD

Trent Wang, MD

Justin Watts, MD

The purpose of this study is to see the effects of an investigational combination treatment of venetoclax, azacitidine, and donor lymphocyte infusion (DLI) in patients with high-risk AML receiving allogeneic hematopoietic cell transplantation, and to assess if the combination treatment is well tolerated and prevents disease relapse after transplant.

Phase 1 dose escalation/de-escalation and dose expansion design.

Venetoclax in Combination With Azacitidine (VEN/AZA) Followed by Donor Lymphocyte Infusion (DLI) for Patients With Very High-Risk Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)

A Phase 1 Study of Venetoclax in Combination With Azacitidine (VEN/AZA) Followed by Donor Lymphocyte Infusion (DLI) for Patients With Very High-Risk Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)

The RP2D of VEN/AZA therapy will be determined as the maximum tolerated dose of study treatment as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

The number of participants experiencing treatment-related toxicity. Toxicity is defined as including dose limiting toxicities (DLTs), serious adverse events (SAEs) and adverse events (AEs) in study participants after starting study therapy. Toxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

Recurrence-free survival (RFS) is defined as the elapsed time measured in months between the treatment start date (Cycle 1 Day 1) and date of documented disease recurrence or death from any cause. Alive patients without recurrence will be censored at the date of last documentation of recurrence-free status.

Overall survival (OS) is defined as the elapsed time measured in months between the treatment start date (Cycle 1 Day 1) and date of death from any cause. Alive patients will be censored at the date last known to be alive.

Treatment-related Mortality (TRM) is defined as the proportion of participants that died after starting study therapy, during the time of observation and in the absence of disease progression.

The number of participants with acute graft-versus-host disease (aGVHD) among study participants will be reported at +100 and +180 days post-allogeneic HCT.

The number of participants with chronic graft-versus-host disease (cGVHD) among study participants will be reported at one (1) year post-allogeneic HCT.

Antonio M Jimenez Jimenez

Associate Professor of Clinical

Graft vs Host Disease

Preleukemia

Myelodysplastic Syndromes

Syndrome

Bone Marrow Diseases

Precancerous Conditions

Homologous Wasting Disease

Micronutrients

Vitamins

Ascorbic Acid

Trace Elements

Antioxidants

Protective Agents

Vitamin C

All study participants will receive the same treatment. Each participant will be given intravenous, which means by vein (IV), vitamin C three times a day for 14 days. Then participants will take vitamin C orally (by mouth in pill form) twice a day each day until 6 months after transplant. The treatment is IV vitamin C 50 mg/kg/day. After completion of the IV vitamin C doses, oral vitamin C 500 mg twice each day.

Intravenous (IV) vitamin C 50 mg/kg/day divided in 3 doses beginning on posttransplant Day +1 and continuing through Day +14; each dose (16.7 mg/kg) given in 50 mL of 5% dextrose and water over 30 minutes every 8 hours

• After completion of the IV vitamin C doses, oral vitamin C 500 mg twice each day beginning on Day +15 and continuing until Day +180

Intravenous (IV) and oral Vitamin C

William B Clark, MD

This phase 2 trial studies the effect of intravenous (IV) vitamin C repletion after myeloablative allogeneic stem cell transplant.

Vitamin C is a nutritional supplement that can help fight inflammation. Most patients who have a stem cell transplant have lower than normal levels of vitamin C in their blood. Patients will receive intravenous Vitamin C the day after transplant for two weeks, followed by oral vitamin C until six months after transplant. The effect of the Vitamin C on non-relapse mortality (NRM), time to engraftment, rate of acute graft-versus-host disease and to characterize the safety and tolerability of the vitamin C regimen.

Therapeutic Use of Intravenous Vitamin C in Allogeneic Stem Cell Transplant Recipients

To determine the effect of parenteral vitamin C on non-relapse mortality (NRM) at one year following myeloablative allogeneic HCT. Non-relapse mortality is defined as defined as mortality from complications of HCT but not tumor relapse, is usually from graft versus host disease (GVHD), infection, or organ failure.

To determine the effect of the vitamin C regimen on the time to hematopoietic engraftment.

Percentage of patients with a diagnosis of acute GVHD

The number of participants who have adverse events related to Vitamin C therapy

Virginia Commonwealth University

Adverse Events (AEs) \>/= grade 3 regardless of expectedness or attribution were recorded

All study participants will receive the same treatment. Each participant will be given intravenous, which means by vein (IV), vitamin C three times a day for 14 days. Then participants will take vitamin C orally (by mouth in pill form) twice a day each day until 6 months after transplant. The treatment is IV vitamin C 50 mg/kg/day. After completion of the IV vitamin C doses, oral vitamin C 500 mg twice each day.

Intravenous (IV) and oral Vitamin C: Intravenous (IV) vitamin C 50 mg/kg/day divided in 3 doses beginning on posttransplant Day +1 and continuing through Day +14; each dose (16.7 mg/kg) given in 50 mL of 5% dextrose and water over 30 minutes every 8 hours

• After completion of the IV vitamin C doses, oral vitamin C 500 mg twice each day beginning on Day +15 and continuing until Day +180

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies	NCT05753501	Hematologic Can...	ABBV-101	18 Years -	AbbVie
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies	NCT05753501	Hematologic Can...	ABBV-101	18 Years -	AbbVie
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
Venetoclax in Combination With Azacitidine (VEN/AZA) Followed by Donor Lymphocyte Infusion (DLI) for Patients With Very High-Risk Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)	NCT06158100	Acute Myeloid L...	Venetoclax Azacitidine Donor Lymphocyt...	18 Years - 75 Years	University of Miami
Therapeutic Use of Intravenous Vitamin C in Allogeneic Stem Cell Transplant Recipients	NCT03613727	Lymphoid Leukem... Myeloid Leukemi... Monocytic Leuke... Myelodysplasia	Intravenous (IV...	18 Years - 77 Years	Virginia Commonwealth University

Spots Global Cancer Trial Database for hematopoietic cell transplant (hct)