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

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Daunorubicin

Etoposide phosphate

Asparaginase

Sorafenib

Gemtuzumab

Calicheamicins

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

* Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
* Induction II - MA
* Intensification I - AE
* Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

Participants in this arm will receive standard Aflac-AML Regimen with the following chemotherapy:

* Induction-1: patients will receive gemtuzumab in addition to ADE therapy based on genotyping. Induction I lasts a total of 28 days.
* Induction 1 for FLT3-ITD patients - ADE (10+3+5) with GO with Sorafenib
* Induction II - MA
* Induction II for FLT3-ITD patients - MA with Sorafenib
* Intensification I - AE
* Intensification I for FLT3-ITD patients - AE with sorafenib
* Intensification II - HD ARAC/LASP
* Intensification II for FLT3-ITD patients - HD ARAC/LASP with sorafenib
* Hematopoietic stem cell transplantation (HSCT)

If a patient is classified as High risk after Induction I, they may proceed to best allogenic donor SCT following Induction II. These patients may receive a third course of chemotherapy prior to HSCT. In cases where HSCT is not an option, patients can receive 4 cycles of chemotherapy. Only patients with FLT3-ITD mutation will receive sorafenib.

100 mg/m²/dose every 12 hours IV Days 1-10

25,000 International Units/m²/dose IM Days 2, 9

Erwinase

Administered as a single 3 mg/m2 dose of GO to be given between days 6-10 during Induction I for patients with CC genotype, in addition to ADE therapy.

Gemtuzumab ozogamicin

Transplantation of multipotent hematopoietic stem cells from bone marrow

Stem cell transplantation (SCT)

200 mg/m2/dose daily, rounded to accommodate tablet size. The maximum dose will be 400 mg. Days 7 through 34.

Himalee Sabnis, MD

The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) to approximately 50% and 65% respectively, with current treatment strategies. Patients with good response to induction and/or those who lack high-risk cytogenetic and molecular features \[classified as low-risk AML (LR-AML)\] have even better outcomes with EFS and OS approaching 70% and 85% respectively; however, treatment-related toxicities remain a major concern. Anthracycline-based therapeutic regimens expose patients to the risk of anthracycline-induced cardiotoxicity. Therefore, strategies that reduce cardiac toxicities using tailored approaches while maintaining and/or improving outcomes are needed for all patients with AML. The Children's Oncology Group (COG) regimens AAML1031 and AAML0531 utilized an anthracycline-intensive backbone for LR-AML with cumulative anthracycline doxorubicin-equivalent doses of up to 492mg/m2. However, high-risk patients treated with chemotherapy alone received an intensified induction chemotherapy (using mitoxantrone-cytarabine) but with overall reduced doses of anthracycline-equivalent (342mg/m2). The investigators piloted an institutional practice to treat all LR-AML patients with four cycle regimen (Aflac-AML) with the goal of reducing cumulative anthracycline exposure, thereby reducing the risk of cardiotoxicity, while providing three high-dose cytarabine courses. In this pilot institutional experience with this approach, they were able to maintain excellent outcomes for this low-risk group with 3-year event-free survival (EFS) and OS of 70.0% ± 0.1% and 85.5% ± 0.08% respectively, from end of course 1. Recent evolution in cytogenetic classification has further delineated risk groups in AML. Gemtuzumab ozogamicin (GO), an antibody-drug conjugate was shown to reduce relapse risk in patients with CC genotype with de-novo AML on COG study AAML0531. The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

AflacLL1901 (CHOA-AML)

CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)

Event-free survival defined as the time from on study to death, failure to achieve remission or relapse in newly diagnosed patients with pediatric acute myeloid leukemia in the Low risk stratification group and High risk stratification group

Time from study entry and from end of first course of therapy for newly diagnosed patients with pediatric acute myeloid leukemia

Number of patients that are in remission (MRD negative) after course 1 in participants receiving GO and those that did not receive GO.

Disease-free survival for patients who are MRD negative but lack high or low risk molecular and cytogenetic features, defined as time from end of first course of therapy to death or relapse

Number of patients that develop cardiac ejection fraction \<50% (CTCAE V5.0 grade 2 or greater dysfunction) either during therapy (early cardiotoxicity) or after completion of therapy (late cardiotoxicity)

Number of participants that developed infection and/or febrile neutropenia at the end of each treatment cycle.

Duration of hospital admission in patients that developed infection and febrile neutropenia at the end of each treatment cycle

Emory University

Assistant Professor

Participants in this group received AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype\^ Patients were classified into risk groups following Induction I

* \^If has FLT3-ITD mutation, Sorafenib is added

Induction I

Participants in this group received Mitoxantrone/AraC

Low Risk - Induction II

Participants in this group received Mitoxantrone/AraC\^

* \^If has FLT3-ITD mutation, Sorafenib is added

High Risk - Induction II

Participants in this group received AraC/Etoposide

Low Risk - Intensification I

Participants in this group received HD AraC/Asparaginase

Low Risk - Intensification II

Patients were classified as low risk following Induction I. All were MRD negative without low or high risk genetic and prognostic factors.

* Induction I: AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype
* Induction II: Mitoxantrone/AraC
* Intensification I: AraC/Etoposide
* Intensification II: HD AraC/Asparaginase

Aflac-AML Low Risk Patients

Patients were classified as high risk following Induction I. All were MRD negative with high risk genetic and prognostic factors.

Induction I: AraC/Daunorubicin/Etoposide (10+3+5) +/- GO based on CC genotype\^ Induction II: Mitoxantrone/AraC\^ Intensification:\* AraC/Etoposide\^ OR HD AraC/Asparaginase\^ Allogenic HSCT

* \^If has FLT3-ITD mutation, Sorafenib is added
* \* Depending on timing patients may proceed to HSCT following Induction II or receive Intensification. If HSCT is not an option, patients can receive 4 cycles of chemotherapy

Aflac-AML High Risk Patients

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Himalee Sabnis

Event-free Survival (EFS) in Low Risk Patients and High Risk Patients

Overall Survival (OS)

Patients with CC genotype received Induction 1 AraC/Daunorubicin/Etoposide (10+3+5) with Gemtuzumab ozogamicin (GO)

Induction I With GO

Patients without CC genotype received Induction 1 AraC/Daunorubicin/Etoposide (10+3+5)

Induction I Without GO

Minimal Residual Disease (MRD) Negative Status

Patients who are MRD negative but lack high or low risk molecular and cytogenetic features, defined as time from end of first course of therapy to death or relapse.

Patients Who Are MRD Negative

All patients were MRD negative at the end of Induction I. No patients were assigned low risk due to low risk molecular and cytogenetic features. All high risk patients had high risk molecular and cytogenetic features.

Disease-free Survival (DFS) for Patients Who Are MRD Negative

Early cardiotoxicity

Late cardiotoxicity

The definition of late cardiotoxicity is after completion of therapy. All 3 of the high risk patients came off protocol early and did not complete therapy. For the low risk patients, 2 did not complete therapy. Among the 3 that did complete therapy, 1 patient has been lost to follow-up since completion of therapy with no cardiac data available.

Cardiotoxicity in Patients With de Novo AML That Receive the Four-cycle Aflac-AML Regimen With the Inclusion of Dexrazoxane

Cycle 1 - Induction 1

Cycle 2 - Induction 2

Cycle 3 - Induction 3

Cycle 4 - Induction 4

All 3 of the high risk patients came off protocol early and did not complete therapy. For the low risk patients, 2 did not complete therapy. Among the 3 that did complete therapy, 1 patient has been lost to follow-up since completion of therapy with no cardiac data available.

Proportion of Patients Who Develop Infection and/or Febrile Neutropenia During Each Treatment Course

Duration of Hospital Admission in Patients That Developed Infection and Febrile Neutropenia at the End of Each Treatment Cycle

Overall Study

Venetoclax

Azacitidine

Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)

Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).

Participants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)

Subcutaneous (SC) or intravenous (IV) injection

BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.

Best Supportive Care (BSC)

ABBVIE INC.

The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid Leukemia (AML) participants compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT).

This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).

A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)

A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine After Allogeneic Stem Cell Transplantation in Subjects With Acute Myeloid Leukemia (AML) (VIALE-T)

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax and AZA as described in the protocol and evaluated by the Investigator and the sponsor.

OS is defined as the number of days from the date of randomization to the date of death from any cause.

Morphologic relapse from AML defined as bone marrow blasts of \>= 5% or reappearance of blasts in the peripheral blood not attributable to any other cause (e.g., bone marrow regeneration) in at least 2 peripheral blood samples at least one week apart or development of extramedullary disease after achieving a complete remission (CR) or complete remission with incomplete count recovery (CRi); or the date of death from any cause, whichever comes first as determined by Independent Review Committee (IRC).

Morphologic relapse from AML, non-morphologic relapse from AML, which is defined as increase in disease burden determined by standard methods with reappearance or acquisition of new findings with or without change in anti-leukemic treatment per investigator decision due to cytogenetic abnormalities or change in molecular marker or measurable residual disease by multiparameter flow with sensitivity to at least 10\^-3; or the date of death from any cause, whichever comes first as determined by IRC.

GRFS is defined as number of days from the date of randomization to occurrence of disease relapse OR incidence of GvHD OR death from any cause.

GvHD rate is defined as grade 2 or higher for acute graft-versus-host disease (aGvHD) and moderate/severe for chronic graft-versus-host disease (cGvHD) assessed by investigator.

The EORTC-QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participantts rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.

MRD conversion rate is defined as percentage of participants who convert to MRD \< 10\^-3 after initiation of treatment.

Time to deterioration defined as number of days from randomization to either deterioration of \>= 5 points based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3 or death due to any cause.

The EQ-5D-5L is a generic preference instrument that has been validated in numerous population and has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. These dimensions are measured on a 5-point scale: with higher scores representing better functioning/quality of life and greater symptom burden.

AbbVie

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Leukemia, Lymphoid

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Lymphocytic, Chronic, B-Cell

Graft vs Host Disease

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Homologous Wasting Disease

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Sirolimus

Temsirolimus

MTOR Inhibitors

Mesna

Antineoplastic Agents, Alkylating

Alkylating Agents

Clotrimazole

Miconazole

Antifungal Agents

Anti-Third Party CTL (Cytolytic T-lymphocytes) with Nonmyeloablative SCT (Stem Cell Transplantation)

Rituximab 375 mg/m\^2 intravenously over several hours on Day -13, followed by 1000 mg/m\^2 intravenously on Days -6, 1, and 8; + Cyclophosphamide 50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine; + Fludarabine 40 mg/m\^2 intravenously over 30 minutes once per day for 4 days, starting Day -6; + Radiation 2Gy Total body radiation day before transplantation + Stem Cell Transplantation + Intravenous infusion of Anti-third Party CTLs.

375 mg/m\^2 intravenously over several hours on Day -13, followed by 1000 mg/m\^2 intravenously on Days -6, 1, and 8.

50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine.

40 mg/m\^2 intravenously over 30 minutes once per day for 4 days, starting Day -6.

10 mg/kg continuous intravenous infusion for 4 hours for total of 6 doses (24 hours) following Cyclophosphamide.

2Gy Total body radiation day before transplantation

Radiation Treatment

Allo CD34+ Selected SCT/Infusion of stem cells.

Stem Cell Transplantation (SCT)

6 mg by mouth on day -2 followed by 2 mg daily from day -1 through day +7.

Intravenous infusion of anti-third party CTL.

Anti-third Party Cytolytic T-lymphocytes (CTL)

Richard E. Champlin, MD

Primary Objective:

1. To determine the maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD (graft-vs-host disease) at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells.

Secondary Objective:

1. Toxicity, response rate, time to progression and overall survival.

GVHD can be a major problem after stem cell transplantation from a healthy donor. It is caused by T-lymphocytes (a type of immune cell) from the donor that can react badly against the person receiving the transplant (the recipient). Researchers want to see if stimulating the donor T-lymphocytes against another person (a third party) and growing them for 28 days will decrease the chance of developing GVHD.

If you are found to be eligible to take part in this study, you will receive the below treatment, including chemotherapy and radiation, before your stem cell transplantation. These include rituximab, cyclophosphamide, fludarabine, and mesna. Rituximab is designed to attach to lymphoma cells, causing them to die. Cyclophosphamide is designed to destroy cancer cells by interfering with their multiplication and slowing or stopping their growth and spread throughout the body. Fludarabine is designed to interfere with DNA repair enzymes so that the leukemic cell cannot repair damaged DNA. This increases the likelihood of the cell dying. Mesna is a drug that lowers the risk of bladder side effects by the cyclophosphamide. Total body radiation is given to to reduce the risk of transplant rejection.

Participants with CLL or lymphoma will receive Rituxan (rituximab) by vein, given over several hours for each dose. The first rituximab dose is 13 days before the transplant. This will be followed by 3 more doses of rituximab, given 6 days before the transplant, and 1 and 8 days after the transplant. All participants will receive fludarabine by vein over 30 minutes once per day for 4 days, starting 6 days before the transplant. All participants will also receive cyclophosphamide by vein over 2 hours. The cyclophosphamide will be given immediately after the first dose of fludarabine. All participants will also receive a continuous infusion of mesna by vein for 24 hours after receiving the cyclophosphamide. One day before transplantation, you will have total body radiation.

After receiving total body radiation, you will receive your stem cell transplantation. On the day of the transplant, you will receive the anti-third party T Lymphocytes (CTLs) by vein. This will be followed by vein infusion of stem cells from the donor. A sample of the anti-third party T-cells cells will also be tested for immune function.

All participants will receive sirolimus by mouth for 10 days, starting 2 days before transplantation. Sirolimus is an immunosuppressive drug which is given to reduce the risk of transplant rejection. You will remain in the hospital for about 4 weeks after the transplant. You will then continue as an outpatient in the Houston area for 100 days after your transplantation, or until your doctor feels it is okay for you to leave the Houston area.

If your disease gets worse after your transplantation, you may receive additional immune cells from the donor (DLI-donor lymphocyte infusion).You may be taken off this study if the transplant does not grow or is rejected, if not enough of the CTLs can be produced, if your disease continues to get worse after receiving additional donors cells, or if you experience any intolerable side effects.

You will have frequent blood tests as medically necessary to evaluate your medical condition. About 3 tablespoons of blood will be collected for immune function testing at 1, 2, 3, 6 and 12 months after the transplant. You will have a bone marrow biopsy, x-rays, and CT scans for evaluation of the cancer at 1, 3, 6, 9, and 12 months after the transplant. The study is over after 1 year. You will be followed-up after that time for routine care, as the doctors feels it is necessary.

This is an investigational study. All of the drugs used in this study, have been approved by the FDA in the treatment of cancer and transplantation. The Miltenyi CliniMACS System which is used to purify stem cells and the anti-third party CTLs has not been approved by the FDA, and its use in this study is experimental. Up to 24 patients will take part in this study. All will be enrolled at M. D. Anderson.

Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Indolent Lymphoid Malignancies

Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Treatment of Indolent Lymphoid Malignancies

Number of participants who achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 \* 109/L. Graft failure is defined as failure to reach an ANC \> 0.5 \* 109/L within 28 days after transplantation with detectable donor cells on chimerism analysis.

Maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 \* 109/L. For dose-finding, "toxicity" is defined as either death or acute GVHD (aGVHD) within 90 days and "response" is defined as the event the patient is alive and engrafted at day 30.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AflacLL1901 (CHOA-AML)	NCT04326439	Acute Myeloid L... AML, Childhood	Cytarabine Daunorubicin Erwinase Etoposide Gemtuzumab ozog... Stem cell trans... Sorafenib	- 21 Years	Emory University
A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)	NCT04161885	Acute Myeloid L... Cancer	Venetoclax Azacitidine Best Supportive...	12 Years -	AbbVie
AflacLL1901 (CHOA-AML)	NCT04326439	Acute Myeloid L... AML, Childhood	Cytarabine Daunorubicin Erwinase Etoposide Gemtuzumab ozog... Stem cell trans... Sorafenib	- 21 Years	Emory University
Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Indolent Lymphoid Malignancies	NCT00473551	Leukemia Lymphoma Myeloma	Rituximab Cyclophosphamid... Fludarabine Mesna Radiation Treat... Stem Cell Trans... Sirolimus Anti-third Part...	18 Years - 70 Years	M.D. Anderson Cancer Center
A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)	NCT04161885	Acute Myeloid L... Cancer	Venetoclax Azacitidine Best Supportive...	12 Years -	AbbVie

Spots Global Cancer Trial Database for stem cell transplantation (sct)