Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
This phase II trial studies how well low-intensity chemotherapy and ponatinib work in treating patients with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia that may have come back or is not responding to treatment. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with rituximab and blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Granulocyte colony stimulating factor helps the bone marrow make recover after treatment. Giving low-intensity chemotherapy, ponatinib, and blinatumomab may work better in treating patients with acute lymphoblastic leukemia.
NCT03147612 — Acute Lymphoblastic Leukemia
Status: Active, not recruiting
http://inclinicaltrials.com/acute-lymphoblastic-leukemia/NCT03147612/
Continuous Glucose Monitoring (CGM) Versus Oral Glucose Tolerance Test (OGTT) Versus T2* MRI Of The Pancreas In High-Risk Group (Hemoglobinopathies, Lymphoma & Acute Lymphoblastic Leukemia): A Comparative Study
A prospective, observational, comparative study with no intervention.The objective of the study to compare the efficiency of detecting glycemic abnormalities using Continuous Glucose Monitoring (CGMs) versus Oral Glucose Tolerance Test (OGTT) and HbA1C (Glycated Hemoglobin) and their relation to iron overload detected by T2* MRI of the pancreas in high-risk patients due to insulin deficiency (potential beta cell injury) and those with insulin resistance and to study the different factors that may affect the glycemic control in these patients in relation to their results like the Dose of corticosteroids and chemotherapy in ALL and Hemoglobinopathies, Liver function in ALL and Hemoglobinopathies, and Serum ferritin in Hemoglobinopathies and their transfusion status. Using Validated Tools with Permission, the participants will be selected through probability (random) sampling method with expected subjects numbers ALL/L: 30-50, Thalassemia Major: 20, Sickle cell disease: 20.
NCT03141398 — Lymphoma
Status: Withdrawn
http://inclinicaltrials.com/lymphoma/NCT03141398/
A Retrospective Study to Evaluate the Hematological Remission Rates and Survival Among Chinese Adult Patients With Relapsed or Refractory B-precursor Acute Lymphoblastic Leukemia(ALL)
Although the response rate by first-line treatment has been improved, most adult patients with relapsed or refractory ALL will eventually relapse with poor outcomes regardless of treatments. To further understand current status of the treatment of adult patients with relapsed or refractory ALL in China, the study retrospectively collected diagnosis and treatment data from ALL patients in 14 centers in China. Primary objective: to estimate the proportion of patients in overall response rate (ORR) for early relapsed or primary refractory Philadelphia chromosome negative (Ph-) B-precursor ALL patients following salvage treatment (i.e., proportion of patients in hematological complete remission [CR] and CR with partial recovery of blood cells [CRh*]); Secondary objectives included: to estimate the proportion of patients in CR, CRh* and CRi(CR/CRh*/CRi) and the duration of CR/CRh*/CRi, overall survival, duration of CR/CRh*and the proportion of patients receiving allogeneic hematopoietic stem cell transplantation (AlloHSCT) for early relapsed/primary refractory Ph-B-precursor ALL patients following salvage treatment; Exploratory objectives included: to estimate the efficacy in late relapsed Ph- B-precursor ALL (first remission duration > 12 months) patients and in Ph+ B-precursor ALL patients and specific subgroup patients following salvage treatment.
NCT03123887 — B-precursor Acute Lymphoblastic Leukemia
Status: Completed
http://inclinicaltrials.com/b-precursor-acute-lymphoblastic-leukemia/NCT03123887/
A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-Targeted Chimeric Antigen Receptor (CAR)-Modified T Cells Bearing a Human Binding Domain, in Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia
This phase I trial studies the side effects of huJCAR014 in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces. In Stage 1, dose-finding studies will be conducted in 3 cohorts: 1. Aggressive B cell NHL 2. Low burden ALL 3. High burden ALL In Stage 2, studies may be conducted in one or more cohorts to collect further safety, PK, and efficacy information at the huJCAR014 dose level(s) selected in Stage 1 for the applicable cohort(s). There are two separate cohorts for stage 2: 1. Cohort 2A, CAR-naïve (n=10): patients who have never received CD19 CAR-T cell therapy. 2. Cohort 2B, CAR-exposed (n=27): patients who have previously failed CD19 CAR-T cell therapy.
NCT03103971 — Recurrent Adult Acute Lymphoblastic Leukemia
Status: Terminated
http://inclinicaltrials.com/recurrent-adult-acute-lymphoblastic-leukemia/NCT03103971/
Administration of Autologous CAR-T Cells Targeting the CD19 Antigen and Containing the Inducible caspase9 Safety Switch in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia
The body has different ways of fighting infection and disease. No single way is effective at fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study combines both T cells and antibodies to try to create a more effective treatment. This investigational treatment is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD19 antigen (ATLCAR.CD19) administration. In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells makes a piece of an antibody called anti-CD19. This antibody can flow through the blood and can find and stick to leukemia cells because these leukemia cells have a substance on their surface called CD19. Anti-CD19 antibodies have been used to treat people with leukemia but have not been strong enough to cure most patients. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood a piece of it is now joined to the surface of the T cells. Only the part of the antibody that sticks to the leukemia cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD19 chimeric (combination) receptor-activated T cells kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. Preliminary results of giving ATLCAR.CD19 cells to leukemia patients have been encouraging; however, many subjects receiving this treatment have experienced unwanted side effects including neurotoxicity and/or cytokine release syndrome (also referred to as cytokine storm or an infusion reaction). Cytokines are small proteins that interreact as e signals to other cells and are the way cells talk to one another. During cytokine release syndrome, too many cytokines are released and too many cells in your body react to their release. Symptoms resulting from cytokine release syndrome vary from flu-like symptoms to more severe side effects such as cardiac arrest, multi-system organ failure or death. We predict that about 50% of patients on this study will experience mild to severe cytokine release syndrome. To help reduce cytokine release syndrome symptoms in future patients, a safety switch has been added to the ATLCAR.CD19 cells that can cause the cells to become dormant or "go to sleep". The safety switch is called inducible caspase 9 or iC9. The modified ATLCAR.CD19 cells with the safety switch are referred to as iC9-CAR19 cells. The purpose of this study is to determine whether receiving the iC9-CAR19 cells is safe and tolerable (there are not too many unwanted effects). Researchers has previously tested different doses of the iC9-CAR19. An effective dose that had the least number of unwanted side effects in patients was identified. It was planned to test this dose in more patients to learn more about its effect in the body. This type of research study is called a dose expansion study. It will allow the investigators to collect more information about the effect of this dose in treating of certain type of cancer.
NCT03016377 — Acute Lymphoblastic Leukemia
Status: Recruiting
http://inclinicaltrials.com/acute-lymphoblastic-leukemia/NCT03016377/
International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones
This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.
NCT03007147 — Acute Lymphoblastic Leukemia
Status: Recruiting
http://inclinicaltrials.com/acute-lymphoblastic-leukemia/NCT03007147/
A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.
NCT02981628 — Recurrent B Acute Lymphoblastic Leukemia
Status: Recruiting
http://inclinicaltrials.com/recurrent-b-acute-lymphoblastic-leukemia/NCT02981628/
A Phase 2, Open-label, Multiple Cohort, Single-arm, Multi-center Trial to Determine the Safety, Feasibility and Efficacy of JCAR015 in Adult Subjects With B-cell Acute Lymphoblastic Leukemia.
This is a single-arm, multi-center, open-label, Phase 2 study to determine the efficacy and safety of JCAR015 in adult subjects with B-cell ALL. The study is divided into two sequential parts, Part A and Part B; subjects will be screened and will provide informed consent before initiating any study procedures in Part A of the study.
NCT02973191 — Precursor Cell Lymphoblastic Leukemia-Lymphoma
Status: Withdrawn
http://inclinicaltrials.com/precursor-cell-lymphoblastic-leukemia-lymphoma/NCT02973191/
Phase 2 Study of CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19) for Adult Patients With Minimal Residual Disease During Upfront Treatment for Acute Lymphoblastic Leukemia
This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART19" cells) in adults with minimal residual disease (MRD) during upfront treatment for CD19+ acute lymphoblastic leukemia.
NCT02935543 — Leukemia, Acute Lymphoblastic
Status: Terminated
http://inclinicaltrials.com/leukemia-acute-lymphoblastic/NCT02935543/
A Phase 1-2 Study of 6-Thioguanine in Combination With Methotrexate and 6-Mercaptopurine During Maintenance Therapy of Childhood, Adolescent, and Adult Lymphoblastic Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukaemia (ALL) is the most frequent cancer in children. The survival rate has improved significantly during the last decades, but the treatment still fails to cure 15 % of the patients. Within the Nordic/Baltic countries, children are treated according to the same protocol, i.e. NOPHO ALL-2008 protocol. Children and adolescents with Lymphoblastic Non-Hodgkin's Lymphoma (LBL) are treated in accordance with the EURO-LB 02 protocol, whereas adults with Lymphoblastic Non-Hodgkin's Lymphoma in Denmark are commonly treated in accordance with the NOPHO ALL-2008 protocol. The longest treatment phase in both protocols is maintenance therapy, which is composed of 6-Mercaptopurine (6MP) and Methotrexate (MTX). The cytotoxic property of 6MP relies upon conversion of 6MP into thioguanine nucleotides (TGN), which can be incorporated into DNA instead of guanine or adenine. This incorporation can cause nucleotide mismatching and cause cell death second to repetitive activation of the mismatch repair system. At Rigshospitalet investigators have developed pharmacological methods able to measure the incorporation of TGN into DNA (DNA-TGN). In a Nordic/Baltic study the investigators have demonstrated higher levels of DNA-TGN during maintenance therapy in children with ALL that do not develop relapse (Nielsen et al. Lancet Oncol. 2017 Apr;18(4)). Preliminary studies indicate that the best approach to obtain DNA-TGN within a target range could be a combination of 6MP, MTX and 6-thioguanine (6TG), as 6TG more readily can be converted into TGN. This study aims to explore if individual dose titration of 6TG added to 6MP/MTX therapy can achieve DNA-TGN levels above a set target above 500 fmol/µg DNA, and thus can be integrated into future ALL and LBL treatment strategies to reduce relapse rates in ALL and LBL. The investigators plan to include 30 patients, and A) give incremental doses of 6TG until a mean DNA-TGN level above 500 fmol/µg DNA is obtained; and B) analyze the changes in DNA-TGN as well as cytosol levels of TGN and methylated 6MP metabolites (the latter inhibits purine de novo synthesis and thus enhance DNA-TGN incorporation), and C) occurrence of bone-marrow and liver toxicities during 6TG/6MP/MTX therapy.
NCT02912676 — Acute Lymphoblastic Leukemia
Status: Completed
http://inclinicaltrials.com/acute-lymphoblastic-leukemia/NCT02912676/