Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Vasodilator Agents

Urological Agents

Dermatologic Agents

Anticoagulants

Other Dietary Supplements

Cytarabine

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Azacitidine

Decitabine

Melphalan

Nivolumab

Sildenafil Citrate

Tretinoin

Citric Acid

Sodium Citrate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Antiviral Agents

Enzyme Inhibitors

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Keratolytic Agents

Citrate

Nivolumab 1 mg/kg days 1,15 iv q28days Fludarabine 25 mg/m2 days 1-3 iv q28days Cyclophosphamide 300 mg/m2 days 1-3 iv q28days

Nivolumab 1 mg/kg days 1,15 iv q28days Cytarabine 10 mg/m2 bid days 1-10 sc q28days All-trans retinoic acid (ATRA) 45 mg/m2 po qd

Nivolumab 1 mg/kg days 1,15 iv q28days Cytarabine 10 mg/m2 bid days 1-10 sc q28days Sildenafil 20 mg tid

Nivolumab 1 mg/kg days 1,15 iv q28days Melphalan 2 mg qd days 1-10 q28days

Nivolumab 1 mg/kg days 1,15 iv q28days 5-azacitidine 75 mg/m2 days 1-7 q28days

1 mg/kg by vein on Days 1 and 15 of a 28 day cycle

75 mg/m2 subcutaneously on Days 1-7 of a 28 day cycle

25 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle. Dose reduction to 15 mg/m2 is permitted in cases of grade 4 hematological toxicity after first cycle.

300 mg/m2 by vein on Days 1, 2 and 3 of a 28 day cycle.

10 mg/m2 subcutaneously two times a day on Days 1-10 of a 28 day cycle

45 mg/m2 per os daily during the whole course of treatment

all trans retinoic acid

20 mg per os three times a day during the whole course of treatment

Sildenafil

2 mg per os daily during the whole course of treatment

There is evidence of involvement of checkpoint pathways, including PD-1, in the pathogenesis and resistance of myelodysplastic syndrome (MDS). However monotherapy with checkpoint inhibitors was ineffective in a number of studies, indicating the presence of several mechanisms of resistance. This pilot study evaluates the safety and preliminary efficacy of nivolumab combination with currently existing treatments in MDS patients who failed at least one line of therapy. The study evaluates if there is a combination which induces objective responses.

Nivolumab With Chemotherapy in Refractory MDS

Pilot Open-label Trial of Nivolumab Combined With Chemotherapy in Refractory Myelodysplastic Syndromes.

Overall response rate (ORR) defined as complete response plus partial response (CR + PR) and hematological improvement (HI). MDS International Working Group criteria will be used to assess response.

Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).

Incidence of severe bacterial, fungal and viral infections incidence based on laboratory confirmation and attending physician assessment

St. Petersburg State Pavlov Medical University

Vice-director for science, R.M. Gorbacheva memorial institute

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antibodies

Immunoglobulins

Interferons

Nivolumab: 3mg/kg intravenously on day 1.

All-trans retinoic acid (Vesanoid) 45 mg/m2 on days 1-14. The dose of Vesanoid can be increased with addition of 15 mg/m2 in next course of treatment if there is no severe adverse effects. Therefore, the dose of Vesanoid could be 60 mg/m2 from the second course, 75 mg/m2 from the third course, till the maximal dose of 150 mg/m2 if patients tolerated the treatment. The decision of dose escalation is left to in-charge physician.

The treatment cycle will repeat every 2 weeks.

Nivolumab, an immune checkpoint inhibitors targeting PD-1, represents a popular treatment option for patients with cancers via immunological mechanism. However, previous studies using nivolumab alone in pancreatic cancer have failed.

Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. All-trans retinoic acid represses ADAR1, a member of interferon-stimulated genes and a negative regulator of IFNs signaling. On the other hand, all-trans retinoic acid simultaneously increases PD-L1 expression for cancer cells to evade immune surveillance. Since combination of anti-PD1 antibody and all-trans retinoic acid may block self-regulating negative feedback loops of IFNs response, this therapeutic strategy may improve outcomes of pancreatic adenocarcinoma patients.

Li-Yuan Bai

This study is to examine the anticancer activity of the combination therapy with all-trans retinoic acid and nivolumab in patients with chemotherapy-refractory advanced or metastatic pancreatic adenocarcinoma.

Pancreatic cancer is an aggressive and lethal disease. Even two combination regimens, FOLFIRINOX and albumin-bound paclitaxel in combination with gemcitabine, are superior to gemcitabine alone as the first-line treatments, the prognosis of patients with locally advanced or metastatic pancreatic cancer remains poor, with a median overall survival of 8 to 11 months and an estimated 2-year survival of only 2%. Even more, there is currently no available treatment proven beneficial for patients who fail the second-line therapy with liposomal irinotecan in combination with 5-FU.

Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a popular treatment option for patients with some kinds of cancers, but previous studies in pancreatic cancer have failed. One critical challenge for immunotherapy in pancreatic cancer is to find efficient therapeutic approaches to reverse this "cold" tumor into a "hot" tumor. Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. Set-to-set genetic analysis revealed that genes regulated by all-trans retinoic acid were predominantly involved in immune response including interleukin-6, tumor necrotic factor-α, IFNs signaling, and PD-L1. Furthermore, mice bearing pancreatic cancer treated with combination of anti-PD-1 and all-trans retinoic acid had a significantly longer survival compared to mice treated with anti-PD-1 or all-trans retinoic acid alone.

Based on the previous findings, we propose this pilot, compassionate use of combination therapy with all-trans retinoic acid and nivolumab for patients with locally advanced or metastatic pancreatic adenocarcinoma who are refractory to current available treatment. This study will also examine ADAR1 as a novel prognostic and predictive biomarker for pancreatic adenocarcinoma patients. This study will help to delineate the role of ADAR1 as a predictive biomarker for immunotherapy, all-trans retinoic acid as a suppressor of ADAR1, and most importantly, the combination of all-trans retinoic acid and nivolumab as an effective anticancer therapy for patients with pancreatic adenocarcinoma.

Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer

Treatment With Nivolumab and All-trans Retinoic Acid for Patients With Refractory Pancreatic Cancer

The median duration of time from the time of registration until death

Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if either of the following outcomes is achieved:

1. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
2. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The median duration of time from the time of registration until disease progression or death. Disease progression is assessed using RECIST 1.1 criteria.

China Medical University Hospital

Leukemia

Leukemia, Promyelocytic, Acute

Neoplasms by Histologic Type

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Arsenic Trioxide

Daily oral NRX 195183 administration for 90 days to assess CR rate. Patients with CR may continue maintenance therapy after a 2-week drug holiday. Maintenance therapy will consist of two 3-month daily oral NRX 195183 administration separated by a 2-week drug holiday.

NRX 195183 Soft Gelatin Capsule

Nonna Snider, BS/BA

Linda Gero

Victoria Chua

The purpose of this study is to determine whether NRX 195183 is effective in the treatment of relapsed or refractory Acute Promyelocytic Leukemia

A common current therapeutic approach to APL uses oral ATRA and chemotherapy in induction and consolidation. This approach has significantly improved survival in newly diagnosed APL patients. However, approximately 30% of patients relapse. Recently, an approach involving the combination of oral ATRA and arsenic trioxide has been tested. The prognosis for relapsed patients is very poor. This study seeks to investigate NRX 195183 monotherapy in patients who have failed or are resistant to or are intolerant of any prior therapy.

Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia

Phase II Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia

NuRx Pharmaceuticals, Inc.

Roshantha A. Chandraratna, PhD, MBA, Chief Scientific Officer

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Respiratory System Agents

Valproic Acid

Theophylline

Neurotransmitter Agents

Bronchodilator Agents

Anti-Asthmatic Agents

ATRA for 14 days, continuous treatment with valproic acid and theophyllin

All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14

all-trans retinoic acid (ATRA)

Valproic acid, highest dose without side effects from day 3 until progression

Valproic acid

Theophyllin, targetted serum level 50-100 from day 3 until progression

Theophyllin

Oystein Bruserud, MD

Hypothesis: Differentiation induction therapy in acute myelogenous leukemia (AML) can be used to achieve disease control and stabilize peripheral blood counts in patients with acute myelogenous leukemia.

Adult patients (\<18 years of age) who can be included: Elderly patients (\>60 years of age) with newly diagnosed AML who cannot achieve standard chemotherapy, patients with relapsed or resistant AML. Patients with relapsed or resistant AML who cannot receive intensive chemotherapy.

Treatment: Patients will be treated with all-trans retinoic acid (oral administration), valproic acid (7 days intravenous administration and later oral administration)and theophyllamine (7 days intravenous administration and later oral administration). Duration of treatment at least 2 months or until disease progression. Maximal duration of treatment 2 years.

Followup: Clinical evaluation, peripheral blood samples, bone marrow samples.

Patients to be included:

1. Elderly patients above 60 years of age with newly diagnosed acute myelogenous leukemia (AML) who cannot receive conventional intensive chemotherapy.
2. Adult patients of any age (\> 18 years of age)with relapsed or resistant AML who cannot receive conventional intensive chemotherapy or allogeneic stem cell transplantation.

We plan to include at least 20 patients, but if possible 30 patients during a 3 years period. The first patient was included November 2004.

Treatment:

All-trans retinoic acid (ATRA) administered orally 22.5 mg/m2 twice daily for 14 days, repeated every third month.

Valproic acid started on day 3 of ATRA therapy, the first week as intravenous administration and later oral administration.

Theophyllamine started on day 3 of ATRA therapy, the first week as intravenous administration and later oral administration.

Duration of treatment at least 2 months unless side effects,until disease progression or an overall duration of treatment of 2 years.

Supportive therapy according to the hospitals general guidelines.

Followup:

The first week treatment in hospital. Later out-patient treatment with regular controls including clinical examination, peripheral blood parameters (including serum valproic acid and theophyllamin levels), bone marrow samples.

Differentiation Induction in Acute Myelogenous Leukemia

Differentiation Induction Therapy for Acute Myelogenous Leukemia

University of Bergen

Professor

Hematologic Neoplasms

Frailty

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle with ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days

ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Han Yue, Ph.D

Wu Depei, Ph.D

Yue Han, professor

This is a randomized, open-label, multicenter study to compare the efficacy and safety of AZA with or without ATRA in newly diagnosed unfit AML or Intermediate,High or Very High Risk MDS

Newly diagnosed unfit AML and Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria are unable to tolerate the intensive chemo-therapy regimens due to their old age and poor physical condition, resulting in limited overall survival. Nowadays, AZA are recommended for unfit acute myeloid leukemia or myelodysplastic syndromes patients with remission rate of 30%\~34%. AZA with or without all-trans retinoic acid (ATRA) can cooperatively inhibit leukemia cell proliferation , induce apoptosis and differentiation.

Aza With or Without ATRA in Newly Diagnosed Unfit AML or Intermediate,High or Very High Risk MDS

Azacitidine in Combination With or Without All-trans Retinoic Acid in Newly Diagnosed Unfit Acute Myeloid Leukemia or Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria

Number of participants (responders) achieving ORR after the 6 cycle treatments，Overall response rate (ORR) based on the International Working Group (IWG)-2006 criteria, which include complete remission (CR), partial remission (PR), and major hematologic improvement (HI).

time from randomization to death from any cause, or last known date to be alive.

Progression-free survival (PFS) will be measured from time of enrolling in the clinical trial to the date on which disease progresses or the date on which the patient dies, whichever comes first.

TI is when the participants who were transfusion dependent on RBC and/or Platelet at baseline achieve transfusion independence post baseline. TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest.

The First Affiliated Hospital of Soochow University

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Bevacizumab

Atezolizumab

Angiogenesis Inhibitors

Growth Inhibitors

* ATRA orally 45 mg/m2 daily in 2 divided doses days 1-7, repeat every 14 days
* Atezolizumab IV D1, 840 mg every 14 days
* Bevacizumab IV D1, 10 mg/kg every 14 days

ATRA orally 45 mg/m2 QD in 2 divided doses days 1-7, repeat every 14 days

all trans Retinoic Acid

Bevacizumab IV D1, 10 mg/kg every 14 days

Simmons Cancer Center CRO Office

Ellen Siglinsky, BS

Syed Kazmi, MD

The main purpose of this clinical trial is to learn about the good and the bad effects of all trans retinoic acid (ATRA), atezolizumab and bevacizumab as a possible treatment for advanced colorectal patients.

Participants will be treated with the following combination of these drugs:

1. ATRA will be given in a pill form to be taken twice a day at home for 7 days starting on day 1 of a cycle.
2. Atezolizumab will be given through a vein in arm or through mediport over 60-90 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW.
3. Bevacizumab will be given through a vein in arm or through mediport over 20-40 minutes every 2 weeks in the outpatient chemotherapy infusion centers at UTSW.

Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Colorectal Cancer

Phase II Single-arm, Single-center Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Refractory Microsatellite Stable Colorectal Cancer

To determine the objective response rate of ATRA, bevacizumab and atezolizumab combination. Complete response+ partial response measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in refractory microsatellite stable (proficient mismatch repair) colorectal cancers

To determine the disease control rate of ATRA, bevacizumab and atezolizumab combination in microsatellite stable (proficient mismatch repair) colorectal cancers. Disease control rate (complete response+ partial response + stable disease) by using RECIST 1.1.

To determine the safety of the combination treatment of ATRA, bevacizumab and atezolizumab combination in microsatellite stable (proficient mismatch repair) colorectal cancers by documenting the Frequency of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab With Chemotherapy in Refractory MDS	NCT03259516	Myelodysplastic...	Nivolumab Azacitidine Fludarabine Cyclophosphamid... Cytarabine all trans retin... Sildenafil Melphalan	18 Years - 80 Years	St. Petersburg State Pavlov Medical University
Nivolumab With Chemotherapy in Refractory MDS	NCT03259516	Myelodysplastic...	Nivolumab Azacitidine Fludarabine Cyclophosphamid... Cytarabine all trans retin... Sildenafil Melphalan	18 Years - 80 Years	St. Petersburg State Pavlov Medical University
Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer	NCT05482451	Effect of Drug	Nivolumab all trans retin...	20 Years - 100 Years	China Medical University Hospital
Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia	NCT00675870	Acute Promyeloc...	NRX 195183 Soft...	18 Years -	NuRx Pharmaceuticals, Inc.
Differentiation Induction in Acute Myelogenous Leukemia	NCT00175812	Acute Myelogeno...	all-trans retin... Valproic acid Theophyllin	18 Years -	University of Bergen
Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia	NCT00675870	Acute Promyeloc...	NRX 195183 Soft...	18 Years -	NuRx Pharmaceuticals, Inc.
Aza With or Without ATRA in Newly Diagnosed Unfit AML or Intermediate,High or Very High Risk MDS	NCT05175508	AML MDS Old Age; Debili... Hematologic Can...	Azacitidine all trans retin...	18 Years - 80 Years	The First Affiliated Hospital of Soochow University
Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Colorectal Cancer	NCT05999812	Colorectal Canc...	all trans Retin... Atezolizumab Bevacizumab	18 Years -	University of Texas Southwestern Medical Center

Spots Global Cancer Trial Database for all trans retinoic acid