Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Leukemia, T-Cell

Leukemia-Lymphoma, Adult T-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, Lymphoid

Lymphosarcoma

Adult T-cell Leukemia/lymphoma

Leukemia, T-cell, Chronic

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Belinostat

Interferons

Peginterferon alfa-2b

Interferon-alpha

Interferon alpha-2

Zidovudine

Interferon-alfa-1b

Antiviral Agents

Immunologic Factors

Antimetabolites

Reverse Transcriptase Inhibitors

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Histone Deacetylase Inhibitors

Belinostat + Zidovudine (AZT) in combination as consolidation therapy, followed by standard zidovudine (AZT)-based maintenance therapy with optional Interferon-Alfa-2b (IFNalfa-2b) or Pegylated Interferon-Alfa-2b (PEG-IFN-alfa-2b)

Belinostat will be administered as 1,000 mg/m2 IV infusion over 30 minutes on Days 1- 5 every 21 days (Exception as per FDA-approved Package Insert: In patients known to be homozygous for the UGT1A1\*28 allele, the starting belinostat dose must be 750mg/m2) for up to 8 cycles.

Zidovudine shall be administered in the outpatient setting as 300 mg tablets orally (PO), three times daily (TID) for 21 days on cycles 1 to 8, followed by maintenance therapy (+/- IFN-alfa) up to the end of Month 12.

OPTIONAL: For subjects receiving interferon therapy at baseline, continue Interferon alfa-2b 5 million IU daily or pegylated interferon alfa-2b 1.5 μg/kg once weekly, subcutaneously (SQ) for up to 12 months.

Interferon-Alfa-2b

Pegylated Interferon-Alfa-2b

Karin Suarez

Juan C Ramos, MD

The investigators propose to use Belinostat in combination with AZT as consolidation therapy for the treatment of ATLL.

Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma

A Phase II Trial of Belinostat as Consolidation Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma

Proportion of participants achieving Complete Molecular Response after receiving protocol therapy. Complete Molecular Response (CMR) is defined as no evidence of disease at any body sites AND the disappearance of malignant clone(s), as proven by negative T-cell receptor gene rearrangement studies of peripheral blood DNA. Molecular response will be evaluated based upon T-cell clonality studies to be conducted while subjects are on Belinostat, and while subjects are receiving AZT-based maintenance treatment (after Belinostat completion).

The proportion of subjects with minimal residual disease (MRD) will also be reported. Minimal Residual Disease (MRD) is defined as the presence of malignant clone(s) as determined by negative T-cell receptor gene rearrangement studies of peripheral blood DNA.

Proportion of participants experiencing treatment-related serious adverse events (SAEs), and adverse events (AEs). SAEs and AEs will be assessed by and assigned severity and treatment attribution using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE), Version 4.03.

Rate of participants achieving complete response (CR) or partial response (PR) to protocol therapy. Response is assessed on the basis of clinical, radiologic, molecular and pathologic (i.e.

bone marrow) criteria.

Subjects will be evaluated during treatment and by follow-up assessments post-treatment. 1-year FFS is defined as the time from study treatment initiation until documented disease progression, relapse after response or death (by any cause, in the absence of progression). In the failure-free subjects, FFS will be censored at the last documented date of failure-free status.

Follow-up for OS post-treatment will occur every 3 months during year 1 post treatment under the proposed study. OS is defined as the elapsed time from study treatment initiation to death or date of censoring. Subjects alive or those lost to follow-up will be censored at the last date known to be alive.

Cytotoxic T-Cell response will be evaluated from serum blood samples, as well as molecular evaluation of ATLL and HTLV-1 clones

University of Miami

Professor

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Heart and Blood Diseases

Musculoskeletal Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Breast Neoplasms

Adenocarcinoma

Pancreatic Neoplasms

Glioma

Osteosarcoma

Sarcoma

Carcinoma, Renal Cell

Neoplasm Metastasis

Lung Neoplasms

Hematologic Neoplasms

Ataxia

Cerebellar Ataxia

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Telangiectasis

Bone Neoplasms

Kidney Neoplasms

Ataxia Telangiectasia

Colorectal Neoplasms

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Neoplasms, Glandular and Epithelial

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Breast Diseases

Skin Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Bone Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pancreatic Cancer

Renal Cell Carcinoma

Soft Tissue Sarcoma

Acute Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Neuroepithelioma

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Irinotecan

Doxorubicin

Liposomal doxorubicin

Lomustine

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Topoisomerase I Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Drugs: Gemcitabine - 21 day cycle. 9-ING-41

Drugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.

Drugs: Paclitaxel. Carboplatin. 9-ING-41.

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

9-ING-41

Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle

Gemcitabine - 21 day cycle

Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.

Doxorubicin.

Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

Carboplatin.

Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle

Nab paclitaxel.

Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.

Paclitaxel.

Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle

Gemcitabine - 28 day cycle

Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

* Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.
* Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.
* Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

9-ING-41 in Patients With Advanced Cancers

Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors

The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 4.03 will be conduced at each protocol-specified timepoint.

To determine the 1-year survival rate of patients treated on the 9-ING-41 schedule chosen from the run-in stage of the study compared to the control arm

Actuate Therapeutics Inc.

Recurrence

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Lenalidomide 25mg by mouth (PO) daily until progressive disease or unacceptable toxicity

25 mg of Lenalidomide administered orally once daily

Toru Sasaki

To evaluate the efficacy of lenalidomide in patients with Adult T-cell Leukemia-lymphoma (ATL) who have previously received chemotherapy for ATL.

A Phase 2 Study of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma

A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma

Time to Response was defined as the time from the first dose of study treatment to the initial documented response (CR or CRu, or PR)

ORR is a Complete Response (CR) + Complete Response unconfirmed (CRu) + Partial Response (PR). A CR requires that target lesions have regressed to normal; nodal non-target lesions have regressed to normal; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are GR 0; peripheral blood is normal; Bone marrow (BM) infiltration is negative and no new lesions. A CRu requires the sum of the product diameters (SPD) of target lesions have decreased by at least 75% from baseline; nodal non-target lesions have regressed to normal size; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are Grade 0; peripheral blood is normal; BM infiltration is "negative" and no new lesions. A PR requires the SPD of target lesions has decreased by at least 50% from baseline; all nodal non-target lesions have regressed to normal or show no increase in size; all extranodal non-target lesions have disappeared

PFS was defined as the time from the first dose of study treatment to progressive disease (PD) or death due to any cause on study or within 28 days after study discontinuation, whichever occurred earlier.

Time to progression was calculated as the time from the first dosing of study treatment to the first documented PD and assessed by the ESEC

Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the start of study treatment and within 28 days after the last dose. Severity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): Grade 1= Mild Grade 2= Moderate Grade 3= Severe Grade 4= Life-threatening and Grade 5= Death related to AE. Serious AEs (SAEs) were those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.

The response duration in participants with an objective response was measured from the date of the first Complete Response or Complete Response unconfirmed or Partial Response to the first date of Relapsed Disease or Progressive Disease (PD). For participants who did not progress during the study, DOR was censored at the last adequate response assessment not showing evidence of PD.

The tumor control rate was measured for those with a response of Complete Remission, + CRu, + PR + Stable Disease (SD) in the EE population based on the best response.

Overall Survival was defined as the time from the start of study treatment to the death due to any cause. For participants who were still alive at the time of the data cutoff, survival data were censored at the latest available date the participant was known to be alive.

Celgene

Lenalidomide 25 mg administered orally once daily (QD) until progressive disease or unacceptable toxicity

Lenalidomide 25 mg administered orally once daily (QD) until progressive disease or unacceptable toxicity.

Age, Continuous

Sex: Female, Male

0 = Fully Active

1 = Restrictive but Ambulatory

2 = Ambulatory but Unable to Work

3 = Limited Self-Care

ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Intent to Treat population was defined as all participants who were enrolled in this study independent of whether they received lenalidomide or not.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Intent to treat population consisted of all participants enrolled independent of whether they received study treatment or not.

Anne McClain, Senior Manager, Clinical Trial Disclosure

The Efficacy Evaluable (EE) population consisted of all participants who met basic protocol requirements (all eligibility criteria) and were evaluated after receiving at least one dose of lenalidomide

Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma	NCT02737046	Adult T-cell Le... ATLL	Belinostat Zidovudine Interferon-Alfa... Pegylated Inter...	18 Years -	University of Miami
Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma	NCT02737046	Adult T-cell Le... ATLL	Belinostat Zidovudine Interferon-Alfa... Pegylated Inter...	18 Years -	University of Miami
9-ING-41 in Patients With Advanced Cancers	NCT03678883	Cancer Pancreatic Canc... Sarcoma Renal Cancer Refractory Canc... Refractory Neop... Refractory Non-... Pancreatic Aden... Resistant Cance... Neoplasm Metast... Neoplasm of Bon... Neoplasm, Breas... Neoplasm of Lun... Neoplasms,Color... Neoplasms Pancr... Malignant Gliom... Malignancies Malignancies Mu... Bone Metastases Bone Neoplasm Bone Cancer Pancreas Cancer Pancreatic Neop... Breast Neoplasm... Acute T Cell Le...	9-ING-41 Gemcitabine - 2... Doxorubicin. Lomustine Carboplatin. Nab paclitaxel. Paclitaxel. Gemcitabine - 2... Irinotecan	18 Years -	Actuate Therapeutics Inc.
Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma	NCT02737046	Adult T-cell Le... ATLL	Belinostat Zidovudine Interferon-Alfa... Pegylated Inter...	18 Years -	University of Miami
A Phase 2 Study of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma	NCT01724177	Adult T-Cell Le...	Lenalidomide	20 Years -	Celgene

Spots Global Cancer Trial Database for atll

Every month we try and update this database with for atll cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for atll

Every month we try and update this database with for atll cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for atll cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.