Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Preleukemia

Myelodysplastic Syndromes

Syndrome

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Disease Attributes

Bone Marrow Diseases

Precancerous Conditions

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Cytarabine

Mitoxantrone

Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

* PD 0332991 will be given orally days 1,2,3
* Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6
* Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose

• PD 0332991 will be given orally days 1,2,3

PD 0332991

Judith Karp, MD

1.1 Primary Objectives

* To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory disease
* To determine the direct cytotoxic effects of single agent PD 0332991 on malignant blasts
* To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone
* To determine if the timed sequential combination of PD 0332991 with ara-C and mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS

1.2 Secondary Objectives:

* To determine the ability of PD 0332991 to directly induce apoptosis in malignant cell populations in vivo
* To obtain pharmacodynamic (PD) data regarding the ability of PD 0332991 to arrest malignant cells in the G 1 phase of cell cycle, followed by synchronized release of those cells into S phase upon discontinuation of PD 0332991 and resultant enhanced ara-C cytotoxicity

A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia

A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias

The number of participants experiencing toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Dose escalation decisions will be based on nonhematologic toxicities in Cycle 1 (28 days) and hematologic toxicities, in the case of an aplastic marrow through Day 56, For cytopenias including ANC \< 500/mm3 or platelets \< 50, 000/mm3 a bone marrow will be performed between days 42 and 49.. Dose limiting toxicity (DLT) will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

The Leukemia and Lymphoma Society

Pfizer

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arm 1

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Ivana Gojo, MD

The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.

To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone

* PD 0332991 125 was given orally days 1,2,3
* Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6
* Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose

Overall Study

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.

Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle.

Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle.

Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Ruxolitinib

Srdan Verstovsek, MD

The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.

The Study Drug:

Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth and survival. By blocking the gene mutation, this may cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 30 participants will be enrolled in the Phase I portion of the study, and up to 136 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ruxolitinib is found.

If you are enrolled in the Phase II portion, you will receive ruxolitinib at the highest dose that was tolerated in the Phase I portion or at a lower dose.

Study Drug Administration:

You will take ruxolitinib tablet(s) by mouth 2 times a day on Days 1-28 of each 28-day study cycle.

You will be asked to keep a diary to record the doses taken. You will be asked to bring your diary and any unused drug to your next visit.

Study Visits:

On Days 1, 7, 14, and 21 of Cycle 1:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* On Day 14 only, you will have a bone marrow aspiration performed to check the status of the disease.

On Day 1 of Cycle 2:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease.

During Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at least every 1-2 weeks. This blood may be drawn at a clinic close to your home.

On Day 1 of Cycles 3, 6, 9, and beyond:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease. On Day 1 of Cycle 3, this will only be done if your doctor thinks it is needed.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-study visit and the follow-up call.

End-of-Study Visit:

After your last dose of study drug, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease.

Follow-Up:

About one month after your end-of-study visit, the study staff will call and ask about any side effects you may be having. This call should last about 5 minutes.

This is an investigational study. Ruxolitinib is FDA approved and commercially available for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. Its use to treat acute leukemia is investigational.

Up to 166 patients will take part in this study. All will be enrolled at MD Anderson.

Phase I is a standard 3+3 design and will be used to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and no formal evaluation of efficacy (response rate will be implemented. Patients in Phase I part who were treated at the MTD will be included toward patients assessed for response in the phase II stage.

Phase l/II Study of Ruxolitinib for Acute Leukemia

A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects With Relapsed or Refractory Acute Leukemia

MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort.

The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy.

Response is defined as complete remission (CR) + complete remission with incomplete blood count (CRi) + Hematologic improvement (HI). Response was to be assessed for participants who were evaluated for the Phase II portion of this study. CR is absolute neutrophil count (ANC) \>/= 1x109/L and platelet count \>/= 100x109/L, absence of leukemia blast cells, normal marrow differential, and complete resolution of extramedullary disease. CRi is CR but platelets are \< 100x109/L or ANC is \<1x109/L. HI is described by the number of individual, positively affected cell lines without the use of growth factors and/or transfusions (lasting at least 4 weeks).

Incyte Corporation

M.D. Anderson Cancer Center

Phase I starting dose of Ruxolitinib 50 mg by mouth twice a day (BID) for 28 day cycle.

Ruxolitinib 50 mg BID

Ruxolitinib 100 mg BID

Ruxolitinib 200 mg BID

Total

Age, Continuous

Srdan Verstovsek, Professor, Leukemia

Number of Participants With Dose Limiting Toxicities (DLTs)

Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Ruxolitinib: Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Maximum Tolerated Dose (MTD) of Ruxolitinib

The study was stopped because of a lack of satisfactory clinical benefit, and did not go on to the Phase II portion. Therefore, data were not collected for this outcome measure.

Participants With a Response

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Chronic Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Azacitidine

Decitabine

Sorafenib

Antimetabolites

Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days; Sorafenib 200 mg orally twice a day.

75 mg/m\^2 subcutaneously (SQ) or by vein (IV) daily for 7 days per 28 day cycle.

Starting dose level 200 mg by mouth two times a day in a 28 day cycle. In Phase II, Sorafenib administered per MTD dose from Phase I. Drug doses separated by approximately 12 hours.

Farhad Ravandi-Kashani, MD

The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can control the disease in patients with AML or MDS. The safety of this drug combination will also be studied.

The Study Drugs:

Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are partly responsible for the abnormal growth and behavior of cancer cells.

5-Azacytidine is designed to activate ("turn on") certain genes in cancer cells whose job is to fight tumors.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive 5-azacytidine either under the skin or by vein on Days 1-7 of each 28-day cycle. If by vein, the infusion will take about 10-40 minutes.

You will take sorafenib by mouth 2 times a day about 12 hours apart, with water on empty stomach, every day.

Each study cycle may last a little longer than 28 days, depending on how you are doing.

Study Visits:

Every week, blood (about 1 tablespoon) will be drawn for routine tests.

Every week for the first 6 weeks, and then as often as your doctor thinks it is needed, you will have your blood pressure measured.

Before each cycle:

* Your performance status will be recorded.
* You will have a physical exam, including measurement of your blood pressure and weight.

Before every 2-4 cycles, you will have a bone marrow aspirate to check the status of the disease.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-treatment and follow-up visits.

End of Study Drug Administration Visit:

After you have stopped taking the study drugs, the following tests and procedures will be performed:

* Your medical history will be recorded.
* Your performance status will be recorded.
* You will have a physical exam, including measurement of your blood pressure and weight.
* You will have a bone marrow aspirate collected to check the status of disease.

This is an investigational study. Sorafenib is FDA approved and commercially available for kidney cancer and liver cancer. 5-Azacitidine is FDA approved for the treatment of MDS, but its combination with sorafenib is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome

Phase I/II Study of Sorafenib and 5-Azacitidine for the Treatment of Patients With Refractory or Relapsed Acute Leukemia and Myelodysplastic Syndrome (MDS) - (VZ-MDS-PI-0227)

MTD is defined as highest dose level in which 6 patients treated with at most 1 experiencing a dose limiting toxicity (DLT) during 1st cycle. One cycle of therapy is 7 days of azacitidine (AZA) and 28 days of sorafenib. Starting dose of Sorafenib is 200 mg twice a day azacitidine

Response according to International Working Group response criteria for Acute myeloid leukemia (AML) (JCO 2003; 21: 4642-9): CR defined by presence of \<5% blasts in the bone marrow (BM), with \>1 X 10\^9/L neutrophils and \>100 x 10\^9/L platelets in the peripheral blood (PB) with no detectable extramedullary disease. Participants who met the above criteria but had neutrophil or platelet counts less than the stated values were considered to have achieved CRi (CR with incomplete recovery of PB counts) or CR with incomplete platelet recovery (CRp) if CR but platelets \< 100 x 10\^9/L but ≥ 50 x 10\^9/L and platelet transfusion independent. Partial response (PR) required all of the hematologic values for a CR but with a decrease of \>/= 50% in the percentage of blasts to 5% to 25% in the BM aspirate.

Bayer

Onyx Therapeutics, Inc.

Celgene

Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.

Phase I: Azacitidine + Sorafenib

Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 400 mg orally twice a day for 28 Day cycle.

Phase II: Azacitidine + Sorafenib

Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib 400 mg orally twice a day for 28 Day cycle.

Phase II: Azacitidine + 400 Sorafenib

Farhad Ravandi-Kashani, Professor, Leukemia Department

Azacitidine + Sorafenib

Phase I: Maximum Tolerated Dose (MTD) of Sorafenib Given With Azacitidine

Complete Response (CR)

Complete Remission Without Platelet Recovery (CRi)

Partial Response

Complete Response (CRp)

No Response

Nine participants were not evaluable for response.

Phase II: Number of Participants With Response

Phase II: Azacitidine + 400 mg Sorafenib

Midostaurin

5-azacytidine 75 mg/m2/d subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 50 mg by mouth twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

Starting dose: 75 mg/m2/d subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle.

5-azacytidine

Starting dose: 50 mg by mouth twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

PKC412

Jorge Cortes, MD

The goal of this clinical research study is to learn if the combination of PKC412 (also called Midostaurin) and 5-azacytidine can help to control refractory or relapsed acute leukemia and MDS. The safety and best dose of the combination of the drugs will also be studied.

The Study Drugs:

PKC412 is designed to block certain receptors (FLT3-Kinase) on cancer cells that are responsible for cancer growth. This may cause the cancer cells to die.

5-azacytidine is designed to cause changes to certain genes that are thought to participate in causing leukemia. These changes are thought to silence these genes so they cannot contribute any longer to sustain the growth of leukemia and MDS.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a part of the study based on when you join.

* If you are one of the first 6 participants, you will receive a pre-planned dose of the study drugs. If 2 participants experience severe side effects, the rest of this group will receive a lower dose.
* If you are not one of the first 6 participants, and fewer than 2 patients had severe side effects in the first group, you will receive the drugs at a higher dose than the first 6 participants.

Study Drug Administration:

You will receive 5-azacytidine by vein over about 30 minutes or through a needle under your skin on Days 1-7 of each 28-day study cycle. Your doctor will decide if you will get the drug by vein or under the skin. You will be required to return to MD Anderson for the first 7 days of every cycle to receive 5-azacytidine.

On Days 8-21 of cycle 1, you will take PKC412 capsules by mouth 2 times a day. Starting with Cycle 2, you will take PKC412 capsules by mouth every day. The research staff will tell you how to take the study drug and you will also be given instructions.

If you have severe side effects from the study drug, the study doctor may decide to stop drug dosing until your side effects improve.

Study Visits:

At every visit, you will be asked about any side effects you have experienced and to list any drugs you may be taking.

* At the start of Cycles 1-2 (+/- 4 days) and then every 2-3 cycles, you will have a complete physical exam.
* Every week during Cycles 1-3 (+/- 4 days) and then every 2-4 weeks, blood (about 1 tablespoon) will be drawn for routine tests and to test your kidney and liver function.
* On Day 28 of Cycle 1 (+/- 4 days) and then every 1-3 cycles, you will have a bone marrow aspirate to check the status of the disease.
* On Day 8 (+/- 1 day) of each cycle for the first cycle before initiation of Midostaurin, then before the start of Midostaurin on Cycle 2, then on Day 1 every 2-3 Cycles, you will have an ECG.
* On Days 8, 15, and 21 of Cycle 1 and Day 1 of Cycle 2, blood (about 1 teaspoon) will be drawn for Pharmacokinetic (PK) testing before you take the study drug.

If you stay on study for longer than 6 months, your doctor will decide what tests and procedures you will have and when they will be performed. At least every 6-12 months you will have a bone marrow aspirate.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

This is an investigational study. PKC412 is not FDA approved or commercially available. It is currently being used for research purposes only. 5-azacytidine is FDA approved and commercially available for the treatment of patients with MDS. The combination of these drugs to treat refractory or relapsed acute leukemia and MDS is investigational.

Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.

PKC412 and 5-Azacytidine

A Combination of PKC412 and 5-Azacytidine for the Treatment of Patients With Refractory or Relapsed Acute Leukemia and Myelodysplastic Syndrome (MDS)

Criteria for response per international working group for Myelodysplastic Syndrome (MDS) \& acute myeloid leukemia (AML) where responders obtained a complete remission (CR), a CR with incomplete bone marrow recovery (CRi), a morphologic leukemia-free status (MLFS), or a partial remission (PR). CR: \<5% bone marrow blasts, neutrophil count\>1.0 X10⁹/L, \& platelet count\>100 X10⁹/L. CRi: all CR criteria except residual neutropenia (\<1.0 X10⁹/L) or thrombocytopenia (\<100 X10⁹/L). MLFS: \<5% blasts in bone marrow regardless of neutrophil \& platelet count in peripheral blood. PR: all CR criteria, except reduction\> 50% in bone marrow blasts, but still \>5%. Clinical responses evaluated using RECIST version 1.1 criteria after every two cycles, with confirmation of clinical response at 4 weeks after achieving response.

Overall response defined as number of participants with response as follows: (OR = CR \[complete response (CR) rate\] + CRi \[complete remission with incomplete count recovery\] + PR \[partial remission\] + HI \[hematologic improvement\]) within 6 months of treatment initiation. complete remission (CR), a CR with incomplete bone marrow recovery (CRi), a morphologic leukemia-free status (MLFS), or a partial remission (PR). CR: \<5% bone marrow blasts, neutrophil count\>1.0 X10⁹/L, \& platelet count\>100 X10⁹/L. CRi: all CR criteria except residual neutropenia (\<1.0 X10⁹/L) or thrombocytopenia (\<100 X10⁹/L). MLFS: \<5% blasts in bone marrow regardless of neutrophil \& platelet count in peripheral blood. PR: all CR criteria, except reduction\> 50% in bone marrow blasts, but still \>5%.

Novartis Pharmaceuticals

Celgene Corporation

AZA 75 mg/m\^2/day subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 25 mg orally twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

Phase I: 5-azacytidine + PKC412 25 mg

AZA 75 mg/m\^2/day SQ or IV on days 1-7 of a 28 day cycle. PKC412 50 mg orally twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

Phase I: 5-azacytidine + PKC412 50 mg

AZA 75 mg/m\^2 on days 1-7 and PKC412 Midostaurin 50 mg bid orally on day 8-21 during the first cycle and continuously thereafter.

Phase II: 5-azacytidine + PKC412

5-azacytidine (AZA) 75 mg/m\^2/day subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 25 mg orally twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

AZA 75 mg/m\^2 on days 1-7 and Midostaurin 50 mg bid orally on day 8-21 during the first cycle and continuously thereafter.

Jorge Cortes, MD/Professor, Leukemia

Complete Remission (CR)

Complete w/Incomplete Bone Marrow Recovery (CRi)

Morphologic Leukemia-Free Status (MLFS)

Partial Remission (PR)

Participant Best Response Assessed Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

Overall Response (OR) Within 6 Months

5-azacytidine 75 mg/m2/day subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 25 mg orally twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

5-azacytidine 75 mg/m2/day subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 50 mg orally twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Chronic Disease

Chronic Myeloid Leukemia

Lymphosarcoma

Chronic Myeloproliferative Disorders

Bortezomib

Belinostat

Histone Deacetylase Inhibitors

Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

bortezomib

belinostat

laboratory biomarker analysis

western blotting

pharmacological study

flow cytometry

Steven Grant

Beata Holkova, MD

RATIONALE: Belinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving belinostat together with bortezomib may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving belinostat together with bortezomib in treating patients with relapsed or refractory acute leukemia or myelodysplastic syndrome.

PRIMARY OBJECTIVES: I. To determine the recommended phase II doses for the combination of bortezomib and belinostat in patients with relapsed or refractory acute leukemia (AL), myelodysplasia (MDS), and chronic myelogenous leukemia in blast crisis. SECONDARY OBJECTIVES: I. Determine safety and tolerance and describe the toxicities of the combination. II. To demonstrate adequate methods for the assessment of pharmacodynamic response of leukemia cells from the bone marrow and/or peripheral blood in terms of effects on NF-kB (nuclear RelA by immunofluorescence microscopy), NF-kB dependent proteins XIAP and Bcl-xL, and BIM, and document pharmacodynamic responses observed in the course of this study. III. To document activity of the combination observed in the course of this study. OUTLINE: Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia	NCT01701375	Relapsed Acute ... Refractory Acut... High-Risk Myelo...	PD 0332991	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase l/II Study of Ruxolitinib for Acute Leukemia	NCT01251965	Leukemia	Ruxolitinib	14 Years -	M.D. Anderson Cancer Center
Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome	NCT01254890	Leukemia	Azacitidine Sorafenib	18 Years -	M.D. Anderson Cancer Center
A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia	NCT01701375	Relapsed Acute ... Refractory Acut... High-Risk Myelo...	PD 0332991	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PKC412 and 5-Azacytidine	NCT01202877	Leukemia	5-azacytidine PKC412	18 Years -	M.D. Anderson Cancer Center
A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia	NCT01701375	Relapsed Acute ... Refractory Acut... High-Risk Myelo...	PD 0332991	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Belinostat and Bortezomib in Treating Patients With Relapsed or Refractory Acute Leukemia or Myelodysplastic Syndrome	NCT01075425	Acute Lymphocyt... Acute Myeloid L... Myelodysplastic... Chronic Myeloge...	bortezomib belinostat laboratory biom... western blottin... pharmacological... flow cytometry	18 Years -	Virginia Commonwealth University
Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome	NCT01254890	Leukemia	Azacitidine Sorafenib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for relapsed acute leukemia