Clinical Research

Protocol 101


Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis

This study is closed.

Verified by Myeloproliferative Disorders-Research Consortium, December 2007


Stem cell transplantation is used to treat may types of diseases. There a 2 types of transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called mini-transplants.


This study proposes to use a conditioning regimen for allogeneic transplantation along with a reduced intensity transplant. Conditioning regiment is the name for the combination of chemotherapy drugs that is given to patients before receiving a transplantation of donor stem cells. It is hoped that the regimen designed for this study proves to be less toxic and has an equal or better anticancer effect than the regimens that are normally used. The regimen being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This regimen has been studied in recipients of matched sibling transplants and in recipients of alternative donor stem cells in other hematologic malignancies. Those subjects, who receive stem cells from an unrelated donor, will also receive and additional drug called ATG or anti thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the recipient rejecting the transplant (graft).


The purpose of this study is to observe if reduced intensity transplants can be used to allow engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this type of transplant is much less toxic than traditional bone marrow transplants. Reduced intensity transplants may be better tolerated by patients who may experience serious side effects from standard (very intense) stem cell transplant.


ELIGIBILITY CRITERIA:

Patients with the following disease: Idiopathic myelofibrosis, or spent PV-, or ET-related myelofibrosis in chronic phase.



Protocol 102


(Europe Only)

Open-Label, Phase 1/2 Study of VELCADEĆĘ (Bortezomib) for
Injection in Subjects with Myelofibrosis with Myeloid Metaplasia (MMM)


This study is closed.

ELIGIBILITY CRITERIA:

Patients must be diagnosed with myelofibrosis requiring therapy.
This includes idiopathic myelofibrosis, post-polycythemic myeloid metaplasia, or post thrombocythemic myeloiod metaplasia. Patients previously treated must have failed at least 1 previous treatment and in the opinion of the investigator requires further treatment. If a subject has had a transplant, he/she must be at least 6 months post-transplant. Any subject who has not received previous therapy and in the opinion of the investigator requires treatment will also be considered for enrollment.



Protocol 103


Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

This study is closed.

Verified by Myeloproliferative Disorders-Research Consortium, April 2008


Myelofibrosis is the gradual replacement of bone marrow (place where most new blood cells are produced) by fibrous tissue which reduces the body's ability to produce new blood cells and results in the development of chronic anemia (low red blood cell count). One of the main distinctions of myelofibrosis is "extramedullary hematopoiesis", the migration or traveling of the blood-forming cells out of the bones to other parts of the body, such as the liver or spleen, resulting in an enlarged spleen and liver.


There is not a standard treatment for myelofibrosis, therefore there is no medication that is specifically used in the treatment of myelofibrosis. Bevacizumab (Avastin®) targets and stops a growth factor in the body that helps produce the type of fibrous tissue that is gradually replacing the bone marrow in the bones.


The purpose of this study is to find out how safe and effective bevacizumab is in treating myelofibrosis. The investigators also wish to find out important biologic characteristics or features of myelofibrosis (how it works and operates) during the time of study participation through an additional correlative biomarker study (MPD-RC #107). The purpose of the biomarker study is to understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases, while the main study is trying to find out how well bevacizumab will work in treating the disease.




Protocol 104


CEP-701 (Lestaurtinib) in Myelofibrosis

This study is closed.

Verified by Myeloproliferative Disorders-Research Consortium, April 2008


Myelofibrosis is the gradual replacement of bone marrow (place where most new blood cells are produced) by fibrous tissue which reduces the body's ability to produce new blood cells and results in the development of chronic anemia (low red blood cell count). One of the main distinctions of myelofibrosis is "extramedullary hematopoeisis", the migration or traveling of the blood-forming cells out of the bones to other parts of the body, such as the liver or spleen, resulting in an enlarged spleen and liver.


Treatment for myelofibrosis is unsatisfactory and there is no medication that is specifically used in the treatment of myelofibrosis. There is a protein that is found to be present in the majority of myelofibrosis patients (JAK2) and the drug Lestaurtinib is being studied to see if it will stop this protein from functioning and thereby help control the disease.


This study is divided into two Phases (1 & 2). In phase 1 we will be looking for the dose of study medication (Lestaurtinib) that will be the highest dose a patient can take without experiencing serious side effects, maximum tolerated dose (MTD).


In phase 2, after the MTD dose has been established in phase 1, we will be investigating how well CEP-701 (Lestaurtinib) works at suppressing the protein (JAK2).


The investigators also wish to find out important biologic characteristics or features of myelofibrosis through an additional correlative biomarker study (MPD-RC #107). The correlative biomarker study is a study that is related to the main study, but is looking to answer different questions than the main study. The purpose of the biomarker study is to understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases, while the main study is trying to find out how well CEP-701 (Lestaurtinib) will work in treating the myeloproliferative disease.






Protocol 105


Familial Myeloproliferative Disorders

This study is currently recruiting participants.

Verified by Myeloproliferative Disorders-Research Consortium, April 2008


Myeloproliferative disorders occur in families, thus giving rise to the theory that it is a genetic disease that may be caused by an abnormal gene in the DNA that can be passed from one generation of family members to another. DNA can be gathered from family members through blood samples and the investigators will investigate (through DNA testing) to see if there are abnormal genes that may be responsible for causing the MPDs. Understanding which genes are responsible for causing MPDs can help develop ways to identify people who may be at risk for developing an MPD, allow for the development of better treatments, possibly a cure, or even prevent the development of MPDs.






MPD-RC 108


Pilot Phase II, Randomized, Double-Blind Placebo Controlled International Study of Clopidogrel and Aspirin for the Treatment of Polycythemia Vera.

This study is closed.

Verified by Myeloproliferative Disorders-Research Consortium, October 2008

The combination of aspirin and clopidogrel may be more effective than aspirin alone in reducing the thrombotic risk in polycythemia vera patients receive hydroxyurea or not. Due to a modest anticipated increase of bleeding events, the dual anti-platelet therapy may have a favorable benefit to polycythemia vera patients at risk for a vascular event.
This is a randomized double-blind controlled trial of patients with polycythemia vera at risk for a thrombotic event who will be randomized to treatment with 75 mg clopidogrel or placebo in addition to low dose aspirin with or without hydroxyurea. Patients will be treated and followed for 6 months plus a 30 day follow-up visit after randomization. Polycythemia vera patients up to the age of 75 will be eligible if they are at increased risk for a thrombotic event or if they have a history of a prior thrombotic event.
The purpose of this study is to evaluate the effect of clopidogrel on leukocyte activation by estimating the difference in reduction of leukocyte activation in patients randomized to clopidogrel (and aspirin +/- hydroxyurea) as compared to patients randomized to placebo (and aspirin +/- hydroxyurea) in polycythemia vera patients.; To evaluate the safety of the combination therapy as compared to the control; to assess the difference between the clopidogrel treated patients and placebo treated patients with regards to the rate of major hemorrhage (any hemorrhage requiring transfusion, hospitalization, or both), minor hemorrhage, and any adverse event leading to permanent discontinuation of treatment will be compared. To estimate the proportion of polycythemia vera patients who are clopidogrel resistant;
The Secondary Objectives is to assess the role of cytochrome P450 2C19 loss-of-function polymorphisms at baseline in relation to the platelet response to clopidogrel as measured by a platelet aggregation response.To assess the role of JAK2 V617F allele burden in influencing leukocyte activation and thromboxane biosynthesis in polycythemia vera patients.


ELIGIBILITY CRITERIA:
Patients must be diagnosed with polycythemia vera. There must be documentation that the patients have met the revised WHO criteria for the diagnosis of polycythemia vera.



MPD-RC 111


Single Arm Salvage Therapy with Pegylated Interferon Alfa-2a for Patients with High Risk Polycythemia Vera or High Risk Essential Thrombocythemia who are Either Hydroxyurea Resistant or Intolerant Or have had Abdominal Vein Thrombosis (Mandatory Companion Protocol MPD-RC 107)
This study is currently recruiting participants.

Verified by Myeloproliferative Disorders-Research Consortium, November 2011
A phase 2 open label clinical trial to evaluate the clinicohematologic response to Pegylated Interferon Alfa-2a separately in three strata of patients with (1) high risk polycythemia vera and (2) high risk essential thrombocythemia who are either refractory or intolerant to hydroxyurea or (3) who have suffered an Splanchnic Vein Thrombosis.
Protocol Treatment: A treatment cycle is defined as a 1 month period of treatment.
Dose Titration and Study Duration
Goal: The goal is to titrate up the dose of the therapeutic agent to the maximal tolerated dose, or that dose which achieves a complete response by LeukemiaNet criteria . Each cycle is defined as 1 month.
Treatment Duration: Patients will be treated for 12 months (with a 3 month confirmation period for a total of up to 15 months) to achieve CR or PR (see section 10.0 definition of response). Those not achieving at least a confirmed PR will stop therapy at 15 months. Length of therapy for responders will be determined by subject’s entrance onto the study. The last subjects to enter the study will continue for at least 24 months and the first subjects entered onto the study could participate for up to 48 months (assuming toxicity or loss of response does not intervene).
Dose Titration of Pegylated Interferon Alfa-2a
1) (Group 1 – no concurrent hydroxyurea) All patients will begin at 45 micrograms/week. Dose will be increased to 90 micrograms per week after the completion of cycle 3 (as tolerated) if one of the following has not occurred.
a. criteria for CR does not already exist and
b. dose limiting toxicity (DLT) does not already exist

2) (Group 2) Patients entering with concurrent hydroxyurea use will begin at 45 mcgs per week. Increase the pegylated interferon alpha dose during the first 2 cycles at a rate that will allow cessation of hydroxyurea prior to initiating cycle 3.

3) Dose titration for both groups 1 and 2 will occur at each monthly visit (or dose reduction in between interval visits (but not dose increases) According to table 2. Interval Dose Levels (0.5, 1.5, and 2.5) are meant to allow titration if toxicity is encountered, and are not steps to be utilized for dose escalation. Dose escalation to levels > 135 micrograms/ week will occur only after 3 months of therapy (unless part of Group 2 and needed for cessation of hydroxyurea). Further fine tuning between dose levels is allowed at site investigators discretion. Levels above +3 likely represent a failure of Pegylated Interferon Alfa-2a and are considered failure of therapy in this trial.

The purpose of this study is To evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response (By LeukemiaNet Criteria) in three strata of patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchnic vein thrombosis.


ELIGIBILITY CRITERIA:

Patients must be diagnosed with diagnosis of ET or PV. There must be documentation that the patients have met the revised WHO criteria . In addition patients must EITHER be intolerant or resistant to Hydroxyurea according to previously modified established criteria.



MPD-RC 112


Randomized Trial of Pegylated Interferon Alfa-2a versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera and High Risk Essential Thrombocythemia Mandatory Companion Protocol MPD-RC 107.


This study is currently recruiting participants.

Verified by Myeloproliferative Disorders-Research Consortium,June 2011.
A randomized open label clinical trial between hydroxyurea and Pegylated Interferon Alfa-2a in two independent disease strata: (1) high risk polycythemia vera and (2) high risk essential thrombocythemia.

Patients in the high risk group of PV or ET will be randomized to treatment with either pegylated interferon alfa-2a or hydroxyurea within strata defined by their disease. Within each disease stratum, patients will be further stratified by prior treatment with hydroxyurea (in past 3 months, Stratum A) or no prior treatment with hydroxyurea (Stratum B).

Dose Titration and Study Duration
Goal: The goal is to titrate up the dose of the therapeutic agent to the maximal tolerated dose, or that dose which achieves a complete response by LeukemiaNet criteria.

Treatment Duration: Patients will be treated for 12 months (with a 3 month confirmation period for a total of up to 15 months) to achieve CR or PR. Those not achieving at least a confirmed PR will stop therapy at the end of 15 months of treatment with pegylated interferon alfa-2a or hydroxyurea. Length of therapy for responders will be determined by subject’s entrance onto the study. The last subjects to enter the study will continue for at least 24 months and the first subjects entered onto the study could participate for up to 48 months (assuming toxicity or loss of response does not intervene).


Dose Titration of hydroxyurea(1 cycle is 1 month for the purposes of titration)

1) Stratum A: Patients randomized to hydroxyurea who enter the trial on hydroxyurea will begin at entry dose assuming:
a. criteria for CR does not already exist and
b. dose limiting toxicity (DLT) does not already exist

2) Stratum B: Patients randomized to Hydroxyurea who enter the trial naďve to hydroxyurea will begin at 500mg twice daily (or 500mg daily if clinically indicated).

4) Dose titration for both groups 1 and 2 will occur at each monthly visit (or dose reduction in between interval visits (but not dose increases) according to table 2. Further fine tuning between dose levels is allowed at site investigators discretion. Levels above +4, or below -3 (if associated with toxicity) likely represent a failure of hydroxyurea.

Dose Titration of Pegylated Interferon Alfa-2a
1) Stratum A: Patients randomized to Pegylated Interferon Alfa-2a and entering with concurrent hydroxyurea will begin at 45 micrograms per week. Increases of pegylated interferon alfa-2a during the first 2 cycles (months) at a rate that will allow cessation of hydroxyurea prior to initiating cycle 3. The goal is to administer a dose of 90 micrograms per week by the end of cycle 6.

2) Stratum B: Patients randomized to Pegylated Interferon Alfa-2a and entering with no concurrent hydroxyurea. All patients will begin at 45 micrograms/week. Dose will be increased to 90 micrograms per week by the completion of cycle 3 (month 3) (as tolerated) if one of the following has not occurred.
a. criteria for CR does not already exist and
b. dose limiting toxicity (DLT) does not already exist

3) Dose titration for both groups 1 and 2 will occur at each monthly visit (or dose reduction in between interval visits (but not dose increases) according to table 3. Interval Dose Levels (0.5, 1.5, and 2.5) are meant to allow titration if toxicity is encountered, and are not required steps in dose escalation. Dose escalation to levels > 135 micrograms/ week will occur only after 3 months of therapy (unless part of Group
2 and needed for cessation of hydroxyurea). Further fine tuning between dose levels is allowed at site investigators discretion. Levels below -3 (if associated with limiting toxicity) or above +3 likely represent a failure of Pegylated Interferon Alfa-2a. Dose levels above
3.0 are considered failure of therapy in this trial.

The purpose of this study is To compare the complete hematologic response rates (By LeukemiaNet Criteria) with Pegylated Interferon Alfa-2a (PEGASYS) vs. Hydroxyurea in two strata of patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia. All comparisons will be carried out separately within each disease stratum.

ELIGIBILITY CRITERIA:
Patients must be diagnosed with diagnosis of ET or PV. There must be documentation that the patients have met the revised WHO criteria.







Protocol 114


Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) with Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis

This study is currently recruiting participants.


The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF).
MF is a disorder in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring.
This study plans to evaluate whether adding the drug Ruxolitinib will further aid in reducing pre-transplant spleen size, improve physical performance levels and reduce adverse events (side effects) related to the transplant.
Ruxolitinib is a drug that is approved by the FDA for the treatment of patients with advanced forms of myelofibrosis.
Using Ruxolitinib prior to stem cell transplantation is experimental.





Protocol 109


Combination Therapy of Ruxolitinib and Decitabine in patients with Myeloproliferative Neoplasms in Accelerated and Blast Phase Disease

This study is currently recruiting participants.


The purpose of this study is to test the safety and tolerability of ruxolitinib at different dose levels in combination with decitabine and the effectiveness of ruxolitinib in combination with decitabine in patients with accelerated or blast phase Myeloproliferative Neoplasm (MPN), which is a group of diseases of the bone marrow in which excess cells are produced.
Ruxolitinib is a drug that is approved by the Federal Drug Administration (FDA) for the treatment of patients with advanced forms of myelofibrosis.
It inhibits the Jak proteins that are often abnormal in MPN.
A recent clinical study showed that ruxolitinib treatment could put some patients with this disease into remission.
Decitabine is a chemotherapy, approved by the Federal Drug Administration (FDA), that has been used to treat acute leukemia.
It works in some patients, but most patients with accelerated and blastic MPN do not respond to treatment.
Ruxolitinib and decitabine will be combined in this study to find out what dose of the two medicines are safe together.
Using Ruxolitinib in combination with Decitabine is experimental. The investigators want to find out what effects, good and/or bad it has on the patient and the disease.





Protocol 115


Open Label Phase I Study of Single Agent Oral RG7388 in Patients with Polycythemia Vera and Essential Thrombocythemia
(With pilot feasibility study in combination with pegylated interferon alfa 2a for patients who do not respond to the single agent at each dose level)


This study is currently recruiting participants.


This research looks at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increase the risk of developing blood clots.
The purpose of Part A of this study is to test the safety and tolerability of drug RG7388 patients and identify the recommended phase II dose in a single agent dose escalation study. The investigators want to find out what effects, good and/or bad it has on the disease.
The purpose of Part B of this study is to test the safety and tolerability of the combination of RG7388 and Pegylated Interferon Alfa-2a or Pegasys in PV/ET patients from Part A who did not achieve at least a partial response by the end of three cycles of single agent RG7388.
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) have been difficult diseases to treat. RG7388 is a selective inhibitor of the p53-MDM2 binding that frees p53 from negative control and activates the p53 pathway in cancer cells, leading to cell cycle arrest and apoptosis in vitro and in vivo. It has been used to treat solid tumors and Acute Myelogenous Leukemia (AML) in clinical trials. Pegasys is a drug that is the standard of care for patients who have Chronic Hepatitis B (CHB).
RG7388 is a drug that is not yet approved by the Federal Drug Administration (FDA) for the treatment of patients with essential thrombocythemia or polycythemia vera. Pegasys is a drug that is approved by the FDA for the treatment of CHB. The use of RG7388 alone and in combination with Pegasys is experimental.






Protocol 106


Research Tissue Bank

This study is currently recruiting participants.

Verified by Myeloproliferative Disorders-Research Consortium, April 2008


This study that will allow for the preservation and/or storage of a small portion one or more of the following tissues:


  • Peripheral blood
  • Bone marrow
  • Bone marrow biopsy
  • A phlebotomized unit of blood
  • Spleen cells
  • Toenail clippings

This material will be used for the study of Myeloproliferative Disorders (MPD) by researchers. The goals of this research study are to understand the causes of MPDs, how to diagnose them more easily and how to treat them better. MPD is a disease affecting hematopoietic stem cells. Hematopoietic stem cells are cells that make blood cells. These stem cells grow in the center portion of the bones called bone marrow. Under some conditions, these cells are also found in blood. There are several diseases, which are classified as MPD. These include polycythemia vera (too many red blood cells), essential thrombocythemia (too many platelets), and idiopathic myelofibrosis (abnormal blood cells and fibers build up in the bone marrow). These syndromes carry a high risk of developing leukemia. It is important to continue to learn more about these blood cancers and to learn more about the effectiveness and potential side effects of various treatments.




ELIGIBILITY CRITERIA:


  • Patients diagnosed with Philadelphia chromosome negative myeloproliferative disorders (MPD):
    polycythemia vera (PV), idiopathic myelofibrosis (IM), and essential thrombocythemia (ET) are eligible.
  • Newly diagnose MPD patients as well as previously treated for a MPD are eligible.
  • Patients currently participating in experimental treatment arms of MPD-RC protocols, or other experimental treatment protocols are not eligible during the period they are on study.

The Samples at time of enrollment that can be donated include: Bone marrow, Buccal swab, Peripheral blood, Spleen cells.



Protocol 107


Correlative Biomarker Study
This study is currently recruiting participants.


Researchers will use abnormal blood and/or bone marrow cells, or materials derived from these abnormal cells, like DNA, RNA, protein or plasma, in laboratory studies. Toenail clippings will provide normal material like DNA for comparison with the abnormal material derived from the blood and/or bone marrow. The results of these studies will be correlated with subjects' disease symptoms and response to their experimental treatment. The MPD-RC researchers are interested in studying molecules from the blood and bone marrow, the exact molecules changing over time with the investigators choosing only the most promising for investigation.


The investigators are attempting to better understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases. These syndromes carry a high risk of developing leukemia. It is important to continue to learn more about these blood cancers and to learn more about the effectiveness and potential side effects of various treatments. It is believed that further basic knowledge about these cancer cells as well as the effects of treatment will lead to the improvement of current therapies and the development of entirely new treatments for these diseases. The MPD-RC is hoping to determine if a number of laboratory tests (biomarkers) will allow for the prediction of response in future patients to the treatment they would receive.



ELIGIBILITY CRITERIA:


  • Patients diagnosed with the following Myeloproliferative disorders including: Polycythemia Vera (PV), Idiopathic Myelofibrosis (IM), and Essential Thrombocythemia (ET) who are participating in treatment protocols of the MPD-RC is eligible.
  • Patients must have signed an informed consent to participate in a Myeloproliferative Disorders Research Consortium (MPD-RC) treatment study to which this protocol is a companion study. The subject must also have signed a consent to participate in this mandatory companion study.

The Samples at time of enrollment that can be donated include: Bone marrow, Peripheral blood.




Posted on June 08 2007 12:28:46 Print