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

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Idarubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.

Participants will receive RO5503781 in escalating doses on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Participants will receive RO5503781 on Days 1 to 5, cytarabine on Days 1 to 7, and anthracycline (daunorubicin or idarubicin) on Days 1 to 3 of each 28-day cycle until disease progression or unacceptable toxicity.

Participants will receive optimized RO5503781 formulation on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).

RO5503781 MBP

Participants will receive RO5503781 tablets daily (new optimized formulation) containing spray-dried powder (SDP) at recommended dose(s) for development from Phase 1b to Phase 3.

RO5503781 SDP

Idarubicin will be administered as per standard clinical practice.

Daunorubicin will be administered as per standard clinical practice.

Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m\^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m\^2 IV infusion daily.

Clinical Trials

This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be administered with cytarabine and anthracycline may be considered . In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.

A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia

A Multi-Center, Open-Label, Phase 1/1b Study of Escalating Doses of RO5503781 Administered Orally as 1) a Single Agent, 2) In Combination With Cytarabine, or 3) With Cytarabine and Anthracycline and 4) Assessing PK and Safety of New Optimized Formulation of RO5503781 With Cytarabine in Patients With Acute Myelogenous Leukemia (AML)

Timeframe for RO5503781: Predose (0 hour \[Hr\]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)

Hoffmann-La Roche

Symptoms and General Pathology

Acute Disease

Disease Attributes

Analgesics

Antirheumatic Agents

Micronutrients

Etoposide

Venetoclax

Mitoxantrone

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Carboplatin

Doxorubicin

Liposomal doxorubicin

Azacitidine

Decitabine

Topotecan

Etoposide phosphate

Thioguanine

Asparaginase

Midostaurin

Sorafenib

Ivosidenib

Clofarabine

Cladribine

Iodine

Cadexomer iodine

Gemtuzumab

Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT

Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.

Iomab-B

Conventional Care

Avinash Desai, MD

The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).

SIERRA is a pivotal Phase 3 randomized controlled study of Iomab-B in Relapsed or Refractory AML patients. The SIERRA trial has a primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival following randomization to Iomab-B, as well as Event-Free Survival. Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning.

Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia

A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)

Defined as CR or CRp lasting 180 days or more from time of initial CR or CRp is documented with evidence of subsequent relapse

Duration of time from randomization to the date of induction treatment failure (ITF), relapse or death

Actinium Pharmaceuticals

Behaviors and Mental Disorders

Immune System Diseases

Aggression

Leukemia, Lymphoid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Accelerated Phase

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Chronic Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Chronic Myeloproliferative Disorders

Participants received MK-8776 10 mg/m\^2 intravenously (IV) on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour continuous intravenous infusion (CIV) on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

Participants received MK-8776 20 mg/m\^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

Participants received MK-8776 40 mg/m\^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

Participants received MK-8776 56 mg/m\^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

Participants received MK-8776 140 mg flat dose IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

MK-8776

Medical Director

This study of SCH 900776 (MK-8776) will evaluate its safety and tolerability when given in combination with cytarabine to participants with acute leukemias. Participants in the Dose-Escalation Part will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of cytarabine. Only one combination treatment cycle of approximately 4 to 6 weeks is anticipated, but participants may receive additional cycles if clinically indicated after discussion between the Investigator and the Sponsor. The recommended combination doses for a Phase 2 trial (RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants will be studied at the combination RP2D.

Study of SCH 900776 (MK-8776) With and Without Cytarabine in Participants With Acute Leukemias (P05247)

A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias (Protocol No. P05247)

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0). DLTs in Cycle 1 consisted of any of the following: 1) Selected Grade 4 drug-related nonhematologic toxicities, 2) Selected Grade 3 drug-related nonhematologic toxicities that do not resolve to ≤ Grade 2 within 48 hours: Neurotoxicity of any duration, Nephrotoxicity of any duration, QT interval corrected by Fridericia (QTcF) prolongation of any duration, 3) Inability to administer Day 10 cytarabine therapy due to ongoing, uncontrolled serious or life-threatening toxicity. The number of participants who experienced a DLT during Cycle 1 is summarized.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who experienced an AE is summarized.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who discontinued study treatment due to an AE is summarized.

Merck Sharp & Dohme LLC

The population consisted of all participants who received at least one dose of study treatment.

Participants received MK-8776 10 mg/m\^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m\^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).

MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2

MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2

MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2

MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2

MK-8776 140 mg + Cytarabine 2 g/m^2

Total

Age, Continuous

Sex: Female, Male

Senior Vice President, Global Clinical Development

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Treatment Due to an AE

Overall Study

Syndrome

Preleukemia

Myelodysplastic Syndromes

Precancerous Conditions

Mocetinostat

Histone Deacetylase Inhibitors

MGCD0103 administered orally three-times per week

MGCD0103

Gregory Reid, MSc, MBA

In this study, MGCD0103, a new anticancer drug under investigation, is given three times per week to elderly patients with previously untreated acute myelogenous leukemia/high risk myelodysplastic syndrome or adults with relapsed/refractory disease.

MGCD0103 in Elderly Patients With Previously Untreated AML/High Risk MDS or Adults With Relapsed/Refractory Disease

A Phase II Study of MGCD0103 (MG-0103) in Patients With Acute Myelogenous Leukemia/High Risk MDS Who Are Elderly and Have Previously Untreated Disease or Who Are Adult and Have Relapsed/Refractory Disease

Mirati Therapeutics Inc.

Bisantrene

Bisantrene 250 mg at final concentration of 0.5 mg/mL will be administrated by intravenous (IV) infusion, delivered by a controlled-rate programmable pump via a central line over 2 hours.

Fludarabine (generic) and Clofarabine (generic) are commercially available as injection for intravenous infusion.

The treatment regimen will comprise daily IV infusion of Fludarabine (Flu), Clofarabine (Clo) and Bisantrene (Xan) administered via central venous line and controlled-rate infusion pump with a 1-hour break between each agent infusion, amounting to a total of 6 hours for each daily FluCloXan treatment in the following sequence:

* First, infusion over 60 minutes of Fludarabine (Flu) at 10 mg/m2
* Followed by infusion of Clofarabine (Clo) at 30 mg/m2 over 60 minutes
* Followed by infusion of Bisantrene (Xan) at 250 mg/m2 over 2 hours.

Arnon Nagler, MD

Arnon Nagler, M.D.

M.D.

An Open-label, Phase II, Two-stage, Study of Xantrene® (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) Lead-in stage: up to 12 (up to 2 cohorts in a 3+3 dose escalation design) Efficacy stage: up to 17 (Simon 2-stage design 9+8)

Study Objectives:

* Confirm safety and tolerability of the combination regimen
* Time to response with combination treatment
* Overall survival

The treatment regimen will comprise daily IV infusion of Fludarabine (Flu), Clofarabine (Clo) and Bisantrene (Xan) administered via central venous line and controlled-rate infusion pump with a 1-hour break between each agent infusion, amounting to a total of 6 hours for each daily FluCloXan treatment in the following sequence:

* First, infusion over 60 minutes of Fludarabine (Flu) at 10 mg/m2
* Followed by infusion of Clofarabine (Clo) at 30 mg/m2 over 60 minutes
* Followed by infusion of Bisantrene (Xan) at 250 mg/m2 over 2 hours. One cycle will comprise daily IV infusion of the combination treatment course for 4 or 5 consecutive days and rest period to between Day 30 and Day 42, based on patient performance and disease status.

Bisantrene Combination for Resistant AML

An Open-label, Phase II, Two-stage, Study of Bisantrene(Xantrene) in Combination With Fludarabine and Clofarabine as Salvage Therapy for Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

To determine the MRD status of patients post completion of FluCloXan. MRD will be asset in patients with defiant mutations by Polymerase Chain Techniques(PCR).

Overall Response Rate (ORR) defined as the proportion of patients with complete remission (CR) and complete remission with incomplete blood count recovery (CRi) between Day 30 to Day 42.

Confirm safety and tolerability of the combination regimen.

Number of months for each patient with no evidence of diseases.

Median surviving months for each patients.

Race Oncology Ltd

Sheba Medical Center

Director Hematology Division

Amino Acids

Gefitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

All patients will receive Gefitinib (Iressa) at a dose of 750 mg orally (three 250 mg tabs) each day.

gefitinib (Iressa) at a dose of 750 mg, once per day

gefitinib

Daniel J DeAngelo, MD, PhD

The purpose of this study is to determine how effective, and to what extent, Iressa is in the treatment of acute myelogenous leukemia.

Patients will receive Iressa daily until either disease progression or intolerable toxicity develops. On Day 1 of treatment, a physical exam and bloodwork will be performed. Once weekly for the first 8 weeks, a physical exam and complete blood count with differential will be performed.

For the first year, a physical exam, bloodwork will be performed monthly. Bone marrow biopsies will be performed after the first month of therapy and then every 3 months for the first year. After the first year a physical exam, bloodwork will be performed every 3 months and bone marrow biopsies every 6 months.

Study of Iressa in Patients With Relapsed or Refractory Acute Myelogenous Leukemia

A Phase II Study of Iressa (Gefitinib), in Patients With Relapsed or Refractory Acute Myelogenous Leukemia and in Older Patients With Newly Diagnosed Acute Myelogenous Leukemia

Brigham and Women's Hospital

Boston Children's Hospital

Dana-Farber Cancer Institute

Principal Investigator

Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle

RO5045377

Multiple escalating oral doses, Days 1 to 5 of each 28-day cycle

20 mg/m2 sc, Days 1 to 10 of each 28-day cycle

cytarabine

1 gm/m2 iv, Days 1 to 6 of each 28-day cycle

This multi-center, open-label, Phase 1b study will evaluate the safety, pharmacokinetics and efficacy of RO5045337 in combination with cytarabine in patients with acute myelogenous leukemia. In Arm A, cohorts of previously untreated patients deemed unsuitable for standard induction therapy will receive escalating oral doses of RO5045377 and cytarabine 20 mg/m2 subcutaneously daily for Days 1 to 10 of each 28-day cycle. In Arm B, cohorts of patients who have relapsed or are refractory after at least one cytarabine/anthracycline containing regimen will receive escalating oral doses of RO5045377 on Days 1 to 5 and cytarabine 1 gm/m2 intravenously on Days 1 to 6 of each 28-day cycle. Patients will receive up to 4 cycles of therapy, patients in Arm A who achieve hematologic response may continue additional cycles until disease progression.

A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

A Multicenter, Open Label, Phase 1B Study of Escalating Doses of RO5045337 Administered Orally, With Cytarabine Administered A) Subcutaneously, or B) Intravenously, in Patients With Acute Myelogenous Leukemia (AML)

RO5429083

1000 mg/m2 iv daily for 5 consecutive days, up to 4 cycles

This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of RO5429083 alone and in combination with cytarabine in patients with acute myelogenous leukemia. In Part A, patients will receive multiple escalating doses of RO5429083 intravenously. In Part B, patients will receive RO5429083 plus up to 4 cycles of cytarabine (1000 mg/m2 iv daily for 5 consecutive days). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

A Study of RO5429083 Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

Open Label, Multicenter, Dose Escalation Phase 1a/b Study of RO5429083, Administered as Intravenous Infusion Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia (AML).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia	NCT01773408	Myelogenous Leu...	RO5503781 MBP RO5503781 SDP Idarubicin Daunorubicin Cytarabine	18 Years -	Hoffmann-La Roche
Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia	NCT02665065	Acute Myeloid L... Leukemia, Acute... Myeloid Leukemi... Leukemia, Myelo... Acute Myelogeno... Leukemia, Acute... Myelogenous Leu... AML Bone Marrow Tra...	Iomab-B Conventional Ca... HCT	55 Years -	Actinium Pharmaceuticals
Study of SCH 900776 (MK-8776) With and Without Cytarabine in Participants With Acute Leukemias (P05247)	NCT00907517	Myelogenous Leu... Leukemia, Lymph... Leukemia, Lymph... Myelogenous Leu...	MK-8776 Cytarabine	18 Years -	Merck Sharp & Dohme LLC
MGCD0103 in Elderly Patients With Previously Untreated AML/High Risk MDS or Adults With Relapsed/Refractory Disease	NCT00374296	Myelogenous Leu... Myelodysplastic...	MGCD0103	18 Years -	Mirati Therapeutics Inc.
Bisantrene Combination for Resistant AML	NCT04989335	Myelogenous Leu...	Bisantrene Fludarabine Clofarabine	18 Years - 65 Years	Sheba Medical Center
Study of Iressa in Patients With Relapsed or Refractory Acute Myelogenous Leukemia	NCT00130702	Myelogenous Leu...	gefitinib	18 Years -	Dana-Farber Cancer Institute
A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia	NCT01635296	Myelogenous Leu...	RO5045377 RO5045377 cytarabine cytarabine	18 Years -	Hoffmann-La Roche
A Study of RO5429083 Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia	NCT01641250	Myelogenous Leu...	RO5429083 cytarabine	18 Years -	Hoffmann-La Roche
A Study of RO5429083 Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia	NCT01641250	Myelogenous Leu...	RO5429083 cytarabine	18 Years -	Hoffmann-La Roche
MGCD0103 in Elderly Patients With Previously Untreated AML/High Risk MDS or Adults With Relapsed/Refractory Disease	NCT00374296	Myelogenous Leu... Myelodysplastic...	MGCD0103	18 Years -	Mirati Therapeutics Inc.

Spots Global Cancer Trial Database for myelogenous leukemia, acute