Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cytarabine

Azacitidine

Tosedostat

Glycine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Neurotransmitter Agents

Participants receive tosedostat PO QD on days 1-28 and cytarabine SC BID on days 1-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Participants receive tosedostat PO QD on days 1-28 and azacitidine IV over 10-40 minutes or SC on days 1-7. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Jorge Cortes

This phase I/II trial studies the side effects and best dose of cytarabine and azacitidine and how well they work when giving together with tosedostat in treating older participants with acute myeloid leukemia or high risk myelodysplastic syndrome. Tosedostat and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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. It is not yet known whether giving tosedostat and cytarabine or azacitidine may work better in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome.

PRIMARY OBJECTIVES:

I. To determine the safety profile of tosedostat (oral) in combination with cytarabine (subcutaneous \[SQ\]) or azacitidine (5-azacytidine) in patients age 60 years or older with relapsed/refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

II. To observe the anti-tumor effects of tosedostat in combination with cytarabine or 5-azacytidine, if any occur.

OUTLINE: This is a phase I, dose-escalation of cytarabine and azacitidine followed by a phase II study. Participants are assigned to 1 of 2 arms.

ARM I: Participants receive tosedostat orally (PO) once daily (QD) on days 1-28 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive tosedostat PO QD on days 1-28 and azacitidine intravenously (IV) over 10-40 minutes or SC for on days 1-7. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants will be followed up at 28 days and then every 3-5 months thereafter.

Tosedostat and Cytarabine or Azacitidine in Treating Older Participants With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Phase I/II Study of Cytarabine or 5-Azacitidine Combined With Tosedostat to Evaluate the Safety and Tolerability in Older Patients With Acute Myeloid Leukemia (AML) or High Risk MDS

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Capecitabine

* The phase I study will be conducted in the standard 6-patient-per-cohort dose de-escalation fashion.
* Tosedostat by mouth daily Days 1-21 of each 21-day cycle. Dose Level 0 (starting dose) = 120 mg PO daily and Dose Level -1 = 60 mg PO daily. All 6 patients in the Phase 1 received 120 mg starting dose of tosedostat.
* Capecitabine 1000 mg/m\^2 by mouth BID Days 1-14 of each 21-day cycle
* Fresh tissue biopsy: Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

* Tosedostat (dose determined by Phase I portion of study) by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine by mouth BID Days 1-14 of each 21-day cycle

Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Fresh tissue biopsy

Andrea Wang-Gillam, M.D., Ph.D.

There are two parts to this study: the goal of the first part of the study is to find the best dose of tosedostat when given in combination with capecitabine. The goal of the second part of the study is to look at how participants respond to treatment with tosedostat and capecitabine.

Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. If 0 or 1 of 6 patients in Dose Level 1 experience DLT during the first cycle, Dose Level 1 will be presumed to be the RP2D.

DLTs are followed through completion of the first cycle.

* Possibly/probably/definitely related to study treatment in 1st cycle (cyc)

  \*Grade (Gr) 4 neutropenia \>7 day, Febrile neutropenia of any duration with temperature ≥ 38.5 °C, Gr 4 anemia requires transfusion therapy on more than 2 occasions in 7 days, Gr 4 thrombocytopenia
* Possibly/probably/definitely related gr. 3/4 non-hematologic toxicity that occurs 1st cyc with the following EXCEPTIONS:

  * Gr 3 nausea/vomiting/diarrhea/anorexia \<72 hours that returns to Gr 1 prior to the start of cyc 2, Gr 3 hand-foot syndrome will only be considered a DLT for patients who have received 1 week of supportive care treatment with no improvement, Gr 3 fatigue that returns to Gr 1 prior to the start of cyc 2, Gr 3 flu-like symptoms \<72 hours that returns to Gr 1 prior to start of cyc 2, Gr 3 arthralgia or myalgias \<72 hours that return to Gr 1 prior to the start of cyc 2, Gr 3 potassium/phosphorus/magnesium that is asymptomatic or of non-clinical significance \<72 hours, Gr 3 hypoalbuminemia

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
* Progressive disease (PD)

  * Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
  * Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

* ORR = Complete response + partial response
* Target lesions

  * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.
  * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
* Non target lesions \*Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).

-Progressive disease (PD)

* Target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
* Non target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase

* CA19-9 is a tumor marker that is used in the management of pancreatic cancer. Rising CA19-9 levels may mean the tumor is growing and decreasing CA19-9 levels may mean the tumor is shrinking or the amount of cancer in the body is decreasing
* A CA19-9 response means that the tumor marker has decreased over baseline (before treatment started) levels

Washington University School of Medicine

Phase I (Tosedostat + Capecitabine)

* Tosedostat (dose determined by Phase I portion of study) by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine by mouth BID Days 1-14 of each 21-day cycle
* Fresh tissue biopsy: Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Phase II (Tosedostat + Capecitabine)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline CA19-9

This outcome measure is for Phase I participants only.

Phase I Only: Recommended Phase II Dose of Tosedostat

Phase I Only: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)

* Tosedostat by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine by mouth BID Days 1-14 of each 21-day cycle
* Fresh tissue biopsy: Patients who have a partial response at the end of cycle 2 will be required to undergo biopsy if deemed safe for the patient and tissue is feasible to obtain.

Phase I and Phase II Combined

Progression-free Survival (PFS) Rate

Overall Response Rate (ORR)

Time-to-progression (TTP)

* Tosedostat by mouth daily Days 1-21 of each 21-day cycle
* Capecitabine by mouth BID Days 1-14 of each 21-day cycle

Phase I and Phase II (Tosedostat + Capecitabine)

Overall Survival Rate (OS)

Number of Participants With a CA19-9 Response

Overall Study

Hematologic Neoplasms

oral, once daily administration of tosedostat to evaluate its efficacy, safety and tolerability

In Part A, approximately 70 subjects will be randomized to one of 2 dose regimens of tosedostat which will be administered orally, once daily. The dose regimens of tosedostat will be:

* 120 mg for 6 months once daily, OR
* 240 mg (induction dose) once daily for 2 months, followed by 120 mg(maintenance dose) for 4 months

In Part B a further 130 subjects will receive the dose regimen of tosedostat identified in Part A as being appropriate, based on the interim analysis during Part A.

Jorge E Cortes, MD

Karen Yee, MD

Eric Feldman, MD

David Rizzieri, MD

Joseph Jurcic, MD

Richard Larson, MD

Hanna J Khoury, MD

Harry Erba, MD

Samir Parekh, MD

Aarthi Shenoy, MD

Anjali Advani, MD

Shambavi Richard, MD

Steven Allen, MD

Ehab Attalah, MD

John Storring, MD

Gerrit J Ossenkoppele, MD

Pieter Sonneveld, MD

Gary Schiller, MD

Peter Westervelt, MD

Julio Hajdenberg, MD

Stuart Goldberg, MD

The purpose of this study is to evaluate the efficacy and safety of tosedostat in elderly patients suffering from refractory or relapsed AML.

There is an urgent need for novel compounds and treatment strategies for elderly patients with AML, particularly those with refractory or relapsed disease for whom there are few effective treatment options. Treatment options for elderly patients are further limited by co-morbidity and tolerability constraints.

Tosedostat is a new aminopeptidase inhibitor, which in preclinical experiments has shown potent activity in both in vitro and in vivo cancer models as a single agent. In early clinical studies particularly good results have been observed in refractory and relapsed AML in older patients and these observations form the basis for the current study.

This multi-center, open label phase II study will enrol approximately 70 subjects in Part A and 130 subjects in Part B.

Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML

The OPAL Study: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of Tosedostat (CHR-2797) in Elderly Subjects With Treatment Refractory or Relapsed Acute Myeloid Leukemia

Quintiles, Inc.

Chroma Therapeutics

Tosedostat 120 mg PO once daily will be administered.

120 mg PO once daily continuously for each 28 day treatment cycle

Gail Roboz, MD

Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (\< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.

This is a single-center, open label, two-arm phase II study of clinical activity of tosedostat in adult patients with MDS who have failed prior hypomethylating agent-based therapy. Arm A is defined as Revised International Prognostic Scoring Systems (IPSS-R) very low, low, and intermediate disease. Arm B is defined as IPSS-R high or very high risk disease. The two arms are separate and will enroll simultaneously. The dose of tosedostat will be 120 mg once a day continuously for each 28 day treatment cycle. Patients will be assessed for disease response, on average, every two cycles as defined in the protocol. If patient has no response as defined by the protocol after two cycles, azacitidine 75 mg/m2 SC or IV for 5 days may be combined with tosedostat, at the investigator's discretion.The primary endpoint the study is to evaluate the safety and efficacy of tosedostat in two groups of patients with myelodysplastic syndrome who have relapsed after or are refractory or intolerant to azacitidine or decitabine. The primary endpoint for patients with IPSS-R very low, low and intermediate disease is transfusion independence and the primary endpoint for patients with high or very high risk disease is overall survival.

Study of Clinical Efficacy and Safety of Tosedostat in MDS

Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Atients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy

Survival following treatment to the date of death, assessed up to a period of 3-4 years.

Overall response according to IWG 2006 criteira

CTI BioPharma

Weill Medical College of Cornell University

Tosedostat 120 mg PO once daily will be administered.

Tosedostat: 120 mg PO once daily continuously for each 28 day treatment cycle

All Patients

Age, Categorical

Dr. Sangmin Lee, MD

Over All Survival

Overall Response

One Year and Two Year Survival

Diseases and Abnormalities at or Before Birth

Neoplasm Metastasis

Congenital Abnormalities

Neoplastic Processes

AML With Myelodysplasia-related Features

Decitabine

Patients receive tosedostat PO QD on days 1-35 and cytarabine IV on days 1-5.

Patients receive tosedostat PO QD on days 1-35 and decitabine IV on days 1-5.

tosedostat

cytarabine

decitabine

John Pagel

This study examines a new oral chemotherapy drug called tosedostat, in combination with cytarabine or decitabine. Tosedostat is thought to work by decreasing the availability of amino acids (building blocks the cell needs to make proteins) in cells. It has been shown in early studies to have activity against a variety of cancers, including leukemias. Patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) with specific genetic mutations have a poorer response to chemotherapy and a higher risk of relapse after treatment. Researchers are looking to see if combinations of chemotherapy drugs may improve outcomes for patients that do not respond as well with the current chemotherapy regimens, without increasing the risks of treatment.

PRIMARY OBJECTIVES:

I. To determine the 4 month survival and complete remission (CR) rates of tosedostat in combination with either cytarabine or decitabine in untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

I. To assess safety and tolerability of tosedostat in combination with either cytarabine or decitabine.

II. To determine the treatment related mortality defined as death within the first 30 days of beginning treatment.

III. To estimate rates of disease-free survival (DFS) and the 1 year overall survival (OS).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tosedostat orally (PO) once daily (QD) on days 1-35 and cytarabine intravenously (IV) on days 1-5.

ARM II: Patients receive tosedostat PO QD on days 1-35 and decitabine IV on days 1-5.

If the patient develops a significant increase in their circulating or bone marrow blast count, the subsequent cycle may be started as early as day 21 of the current cycle. In both arms, treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or partial CR (pCR) may receive 2 additional courses of treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.

Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tosedostat and Cytarabine or Azacitidine in Treating Older Participants With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome	NCT01636609	Acute Myeloid L... High Risk Myelo...	Azacitidine Cytarabine Tosedostat	60 Years -	M.D. Anderson Cancer Center
Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma	NCT02352831	Pancreatic Canc... Cancer of Pancr... Cancer of the P... Pancreas Cancer	Tosedostat Capecitabine Fresh tissue bi...	18 Years -	Washington University School of Medicine
Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML	NCT00780598	Acute Myeloid L... AML	Tosedostat	60 Years -	Chroma Therapeutics
Study of Clinical Efficacy and Safety of Tosedostat in MDS	NCT02452346	Myelodysplastic...	Tosedostat	18 Years -	Weill Medical College of Cornell University
Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML	NCT00780598	Acute Myeloid L... AML	Tosedostat	60 Years -	Chroma Therapeutics
Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome	NCT01567059	Acute Myeloid L... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... de Novo Myelody... Previously Trea... Secondary Acute... Secondary Myelo... Untreated Adult...	tosedostat cytarabine decitabine	18 Years -	Fred Hutchinson Cancer Center
Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome	NCT01567059	Acute Myeloid L... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... de Novo Myelody... Previously Trea... Secondary Acute... Secondary Myelo... Untreated Adult...	tosedostat cytarabine decitabine	18 Years -	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for tosedostat

Every month we try and update this database with for tosedostat 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 tosedostat

Every month we try and update this database with for tosedostat 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 tosedostat 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.