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autologous PB stem cell transplant followed by non-myeloablative allogeneic transplant fr multiple myeloma

PBSC collection: 10 ug/kg/d subQ inj D 5 until completion of collection Auto transpl: 5 ug/kg/d subQ inj D 5 until ANC \>= 1500/uL for 2d or 5000/uL for 1 d Allo transpl: 5ug/kg/d subQ inj D 7 until ANC \> 1000/uL for 3 days Donor pheresis: 10ug/kg/d subQ inj d -5 thru -2

filgrastim

2-8,000,000/kg IV infusion allogeneic transplant 2,000,000/kg IV infusion autologous transplant

CD34+ cells

4g/sq m IV infusion over 1-2 hrs D 1 for auto, and 1g/sq m/d IV infusion over 1 hr on D -4 thru -3 for allo, transplant prep

cyclophosphamide

30mg/sq m/d IVPB over 30 min d -7 thru -3 allo transpl

fludarabine phosphate

200mg/sq m IV infusion over 15-30 min D 2 auto transpl

melphalan

5mg/sq m/d IV infusion D 1,3,\& 6: allo transpl

methotrexate

0.03mg/kg PO bid starting dose, D -1 thru +90, then taper thru D +150

tacrolimus

Kenneth C. Anderson, MD

RATIONALE: Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well autologous peripheral stem cell transplant followed by donor peripheral stem cell transplant works in treating patients with multiple myeloma.

OBJECTIVES:

* Determine whether autologous peripheral blood stem cell transplantation (PBSCT) followed by non-myeloablative allogeneic PBSCT is associated with no more than 20% treatment-related mortality rates at 6 months in patients with multiple myeloma.
* Determine the response rate of patients treated with this regimen.
* Determine the percent donor chimerism in patients treated with this regimen.
* Determine the rate of graft-vs-host disease in patients treated with this regimen.
* Determine the toxic effects of this regimen in these patients.
* Determine the disease-free and overall survival of patients treated with this regimen.
* Determine whether abnormal cytogenetics at presentation correlate with poor response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until peripheral blood stem cell (PBSC) collection is complete.

Approximately 2-4 weeks after PBSC collection, patients receive melphalan IV over 15-30 minutes on day -2. Patients then undergo autologous PBSC transplantation (PBSCT) on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

Approximately 2-4 months after autologous PBSCT, patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 hour on days -4 to -3. Patients undergo allogeneic PBSCT on day 0. Patients receive G-CSF SC beginning on day 7 and continuing until blood counts recover.

Patients receive graft-vs-host disease (GVHD) prophylaxis comprising oral tacrolimus twice daily on days -1 to 90 followed by a taper on days 91-150 and methotrexate IV on days 1, 3, and 6.

After day 120, patients with stable or progressive disease and no evidence of active GVHD may receive donor lymphocyte infusion (DLI) over 2 hours. Patients may receive up to 3 DLIs every 8 weeks.

Patients are followed every 3 months for 3 years, every 6 months for 5 years, and then annually for 15 years.

PROJECTED ACCRUAL: A maximum of 63 patients will be accrued for this study.

Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

Overall and disease free survival will be assessed

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Hypertension

Neoplasm Metastasis

Congenital Abnormalities

Pulmonary Arterial Hypertension

Hypertension, Pulmonary

Myeloproliferative Disorders

Primary Myelofibrosis

Familial Primary Pulmonary Hypertension

Neoplastic Processes

Lung Diseases

Respiratory Tract Diseases

Bone Marrow Diseases

Chronic Myeloproliferative Disorders

Antihypertensive Agents

Platelet Aggregation Inhibitors

Vasodilator Agents

Epoprostenol

Tezosentan

Subjects diagnosed with primary pulmonary hypertension (PPH)

Subjects diagnosed with Primary or Secondary Myelofibrosis

Josef T Prchal, MD

To determine the prevalence of myelofibrosis in patients with primary pulmonary hypertension, and to discover if the fibrosis in these patients is primary (AMM) or secondary.

Pulmonary arterial hypertension: Pulmonary arterial hypertension (PAH) is a disease primarily affecting the small precapillary pulmonary vessels. It is characterized by sustained elevation of the pulmonary vascular resistance (PVR). Without therapy, right heart failure and death eventually occur. PAH occurs in an idiopathic form, primary pulmonary hypertension (PPH), and in association with other disorders such as connective tissue diseases or congenital heart disease (CHD). PAH remains a disease of unknown etiology. Until recently, prognosis for PAH was poor, with a median survival of less than 3 years.

Prostacyclin (PGI2) is the main product of arachidonic acid in all vascular endothelium. It is a potent vasodilator in all vascular beds. In addition, it is a potent endogenous inhibitor of platelet aggregation and smooth muscle growth. The prostacyclin receptor (IP) is located on a variety of cell types, enabling prostacyclin to exert a range of biologic actions by means of raising intracellular levels of cAMP through activation of adenylate cyclase. The stable, freeze-dried salt preparation of prostacyclin is known as epoprostenol and is available for IV administration under the brand name Flolan (Glaxo Wellcome, Research Triangle Park, N.C.). The first randomized clinical trial in PPH showed that epoprostenol improved quality of life, hemodynamics, exercise tolerance, and survival over a 12-week period. Epoprostenol has become the standard of care for patients with advanced PPH. Recently, chronic intravenous epoprostenol has been shown to be an effective therapy to improve long-term quality of life and survival in patients with PPH. Epoprostenol also improves hemodynamics, exercise capacity, and quality of life (but not survival) in PAH associated with CHD and connective tissue disease.

Side effects of epoprostenol infusion include rash, headache, jaw pain, leg pain, diarrhea, nausea, catheter infections, chest pain, anxiety dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, tachycardia, flu-like symptoms, and anxiety/nervousness. Thrombocytopenia is commonly seen in patients with PPH treated with PG12. Occasionally, a decrease in other blood cell lines occurs leading to anemia or pancytopenia. Splenomegaly and hypersplenism are observed at times. While thrombocytopenia has been attributed to the antiplatelet effects of prostacyclin, the pathophysiology of pancytopenia is poorly understood. There are no studies that address thrombocytopenia and other hemopoietic abnormalities in people with pulmonary hypertension receiving epoprostenol. The possibility of myelofibrosis causing these hematologic abnormalities has not been investigated.

Primary myelofibrosis is a myeloproliferative disorder, characterized typically by pancytopenia, splenomegaly, a leukoerythroblastic blood smear, fibrosis on the bone marrow examination, and myeloid metaplasia. Like all myeloproliferative disorders, it is due to somatic mutation and clonal proliferation of hematopoietic progenitors. Fibrosis occurs secondary to cytokines secreted by malignant cells. These patients are symptomatic because of cytopenias. Bone marrow failure and transformation to acute myeloid leukemia is the major reason for mortality in these patients. Elevated blood levels of hematopoietic progenitors (identified by positivity for the CD34 antigen) are well documented and correlates with prognosis. Therefore two major identifying features of primary myelofibrosis as opposed to secondary fibrosis of the marrow are: 1) clonal hematopoiesis and 2) high CD 34 positive hematopoietic precursors.

We therefore hypothesize these two will be normal in patients with secondary myelofibrosis and help us distinguish the two entities.

Clonality Studies: Clonality is based on the principal of X-chromosome inactivation and thus, for clonality studies only females can be used as subjects. It is based on the principal that while female cells have two X-chromosomes, one is randomly inactivated during early embryonic development and thus female tissue is a mixture of cells expressing either paternal or maternal inherited x-chromosome genes. In the first step, DNA analysis will study 5 exonic polymorphisms for the X-chromosome genes which have previously been shown to be useful for these purposes. If any of the five loci is heterozygous then the subject is said to be informative for clonality. Studies which will proceed as follows: The fresh blood platelets and granulocytes will be isolated and the RNA isolated and used later for reverse transcription to cDNA which will then be analyzed for X-chromosome allelic usage ratio by single-stranded conformational polymorphisms (SSCP). If only one allele is expressed in platelets or granulocytes the patient is said to be clonal and favors a diagnosis of myeloproliferative disorder (such as AMM), while polyclonal blood (both X-chromosome alleles expressed in platelets and granulocytes) is compatible with secondary myelofibrosis.

A three-color direct immunofluorescent staining method will be used in the evaluation of CD34+ cells. In our preliminary experience we observed four Flolan treated patients with PPH who had splenomegaly, anemia and/or thrombocytopenia. All of these patients had severe marrow fibrosis. The purpose of this study is to determine whether the incidence of the bone marrow fibrosis in this patient population is primary or secondary, and whether a secondary effect is a fibrosis that would be expected to be transient and resolve after discontinuation of Flolan.

Participating subjects will Patients will undergo the following studies:

1. History and Physical examination
2. Peripheral blood smear
3. Bone marrow examination to determine the presence and severity of fibrosis. The bone marrow specimen taken for diagnostic purposes will be examined by three independent hematologists/hematopathologists in a masked fashion for the presence of fibrosis using routine methods.
4. Blood: 30 cc of blood will be collected for

   1. Clonality studies (female subjects only),
   2. CD34 quantitation.
   3. Further studies will be done to monitor the aberrant trafficking of hemopoietic stem cells, the adhesion molecules, and any disease related genes, such as JAK2V617F and cMPL, if indicated.
   4. The above studies will be repeated in patients undergoing lung transplants at 3 months, 6 months and 1 year after transplantation.

Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder

University of Utah

Syndrome

Preleukemia

Myelodysplastic Syndromes

Precancerous Conditions

Detlef Haase, MD, Prof.

In myelodysplastic syndromes (MDS) the knowledge about chromosomal aberrations is important for diagnosis, pathogenesis, prognosis and treatment. Usually, chromosomal anomalies in MDS patients are detected in bone marrow cells by chromosome banding analyses of metaphases. Alternatively or additionally they can be diagnosed by Fluorescence-in-Situ-Hybridization (FISH). The investigators here present a novel method for cytogenetic monitoring of MDS patients from peripheral blood which is representative for the clone size in bone marrow cells. The purpose of this prospective multicenter non-interventional diagnostic study is to detect and to follow chromosomal aberrations from peripheral blood closely, to assess karyotype evolution, to detect rare abnormalities and to correlate the molecular-cytogenetic results with peripheral blood counts, bone marrow morphology and treatment modalities and responses.

Chromosomal aberrations in myelodysplastic syndromes (MDS) play a major role in diagnostics, pathogenesis, prognosis, and, more recently, in treatment allocations. Chromosomal anomalies can be detected by conventional chromosome banding analyses of bone marrow metaphases and most of them are provable by Fluorescence in situ hybridization (FISH) of circulating CD34+ progenitor cells from peripheral blood. For this prospective multicenter non-interventional diagnostic study sequential FISH analyses are performed on immunomagnetically enriched circulating CD34+ cells from peripheral blood as follows: A "super-panel" with the probes D7/CEP7, EGR1, CEP8, CEP XY, D20, p53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R (all Abbott® probes) is used for initial screening, every 12 months during follow-up and in every case of suspected progression. A smaller "standard-panel" with the probes EGR1, D7/CEP7, CEP8, p53, D20, CEP X/Y, TEL/AML1 - plus if necessary an informative probe of the superpanel- was performed for analyses at short intervals every 2 months in the 1st year and every 3 months during the 2nd and 3rd year. Peripheral blood counts are documented once a month, and full blood counts with the number of peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months in the course of the disease. If a bone marrow biopsy is performed, conventional chromosome banding analyses on bone marrow metaphases and, additionally, FISH analyses of enriched CD34+ bone marrow cells and non-enriched bone marrow cells are performed. The results from peripheral blood are correlated with those of conventional banding and FISH analyses performed on bone marrow samples. The aims of this study are to detect acqired chromosomal aberrations in MDS patients from peripheral blood, to follow these anomalies by frequent analyses, to detect rare aberrations and to observe karyotype evolution from peripheral blood.

Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

Screening and Genetic Monitoring of Patients With MDS Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

At each timepoint of FISH analysis the percentage of aberrant interphase nuclei is measured of all (at least 200) interphase nuclei counted.

University Medical Center Goettingen

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Detlef Haase

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma	NCT00028600	Multiple Myelom... Plasma Cell Neo...	filgrastim CD34+ cells cyclophosphamid... fludarabine pho... melphalan methotrexate tacrolimus	- 64 Years	Alliance for Clinical Trials in Oncology
Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder	NCT00722254	Primary Myelofi... Primary Pulmona... Secondary Myelo... Pulmonary Arter...		18 Years -	University of Utah
Reversible Secondary Myelofibrosis or Clonal Myeloproliferative Disorder	NCT00722254	Primary Myelofi... Primary Pulmona... Secondary Myelo... Pulmonary Arter...		18 Years -	University of Utah
Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells	NCT01355913	Myelodysplastic... Chromosmal Aber... Karyotype Evolu... Rare Abnormalit... Cytogenetic Mon...		18 Years -	Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Spots Global Cancer Trial Database for cd34+ cells

Every month we try and update this database with for cd34+ cells 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 cd34+ cells

Every month we try and update this database with for cd34+ cells 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 cd34+ cells 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.