Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

The purpose of this study is to develop a standard of care treatment using allogeneic stem cells for patients with cancers of the blood.

Further Study Information

Preparative regimen:

The chemotherapy (cyclophosphamide and busulfan) is given with the intent of destroying the bone marrow, eliminating any cancerous and preparing for the transplant of the donor's blood stem cells by suppressing the immune system.

l. Ten days before the transplant (Day 10), subjects will be admitted to the bone marrow transplant unit and placed in isolation to reduce exposure to infections. Isolation will be continued until adequate numbers of cells are present in the blood to fight infection.

2. On day -9, -8, -7, -6 busulfan is given.

3. On day -5, -4, -3, -2 cyclophosphamide is given.

4. On day -1 no therapy is given (day of rest).

5. On day 0 the donor stem cells are given intravenously. Additional cells may be given on day +1 or 2 as needed.

Transplant:

Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents. During this time, they will receive the preparative treatment outlined above. Once they have received the preparative regimen, stem cells will be obtained from the donor and given intravenously.

The new stem cells will replace the bone marrow that was damaged by the treatment for the cancer.

Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will then be transferred from the bone marrow transplant unit and discharged from the hospital when medically ready. Subjects will be expected to return for follow-up to the bone marrow transplant clinic at specific dates as determined by their physician.

Eligibility Criteria

Inclusion Criteria:

• Recipients will be <55 years, will have normal organ function (excluding bone marrow) and will have a Karnofsky activity assessment > 90%.

• Creatinine <2.0 mg/dl for adults; or clearance > 50 ml/min for children

• Bilirubin, AST, ALK <2 x normal.

• Pulmonary function test > 50% of normal.

• MUGA > 45% ejection fraction.

• Recipients with related or unrelated donor matched at the HLA A, B, DRB1 loci, or mismatched related or unrelated (if < 35 years old) at a single HLA A, B, DRB1 locus.

• Recipients will be eligible in one of the following disease categories

• Chronic myelogenous leukemia in accelerated phase or in post blast crisis second or greater chronic phase.

• Accelerated Phase: Patients with hematologic peripheral blood or bone marrow findings meeting standard criteria for CML, but who present with or progress to express any of the following findings are considered as having accelerated phase disease:

• Leukocytosis (WBC greater than 50x109/L) uncontrolled by single agent chemotherapy.

• Thrombocytosis (Platelet count greater than 1x1010/L) uncontrolled by single agent chemotherapy.

• Anemia (hemoglobin less than 8 grams/dl) uncontrolled by single agent therapy.

• Peripheral blood blast percentage between 5 and 30%, uncontrolled by single agent chemotherapy.

• Cytogenetic abnormalities in addition to the Philadelphia chromosome at presentation, or the development of new cytogenetic abnormalities in addition to the Philadelphia chromosome during observation.

• Splenomegaly uncontrolled by single agent chemotherapy.

• Extramedullary disease.

• Severe, progressive myelofibrosis or osteosclerosis.

• Achievement of a "second chronic phase" after blast crisis.

• Acute myelocytic leukemia in first or greater remission, or first, second or third relapse.

• Acute lymphocytic leukemia in the 2nd or greater bone marrow remission.

• High risk children will be transplanted in first remission if they meet one of the following criteria:

• Infants < 6 months at diagnosis;

• Infants < 12 months at diagnosis with one or more of the following:

CD10 negative blasts

• WBC > 100,000/Fl at diagnosis

• M2 or M3 on day 14 bone marrow (M2 = 5-15% blasts; M3 > 15% blasts)

• Children > 12 months <10 years with one of the following:

• High risk cytogenetics: t(9;22), t(4;11) or hypodiploidy (< 45 chromosomes)

• Children and young adults > 10 years < 21 years of age with one or more of the following:

• High risk cytogenetics: t(9;22), t(4;11) or hypodiploidy (< 45 chromosomes) WBC at diagnosis > 200,000/OI

• Any patient with M2 or M3 bone marrow on day 28 of initial induction (i.e. No CR in 4 weeks).

• Patients 21-30 years old are considered high risk and eligible in 1st CR if they have either:

• B-cell ALL (Surface immunoglobulin +) or with t(8;14); t(2;8); or t(8;22).

• High risk Cytogenetic features: t(9;22; t(4;11); or hypodiploidy (< 45 chromosomes).

• WBC at diagnosis > 20,000/Fl;

• No CR by day 28 of initial induction therapy;

• Extramedullary leukemia.

• All patients > 30 years old.

• Myelodysplastic syndrome.

• RAEB: "refractory anemia with excess of blasts" (RAEB)

• Cytopenia affecting 2 or more myeloid lines.

• Less than 5% circulating blasts.

• Bone marrow evidence of dysgranulopoiesis, dyserythropoiesis, and/or dysmegakaryocytopoiesis.

• 20% blasts in the bone marrow.

• A history consistent with the above syndrome for greater than three months prior to bone marrow transplantation.

• RAEB in Transformation:RAEB as defined above with any of the following modifications:

• 5% or more blasts in the peripheral blood.

• 20 30% blasts in bone marrow.

• Presence of Auer rods in granulocytic precursors.

• Severe Cytopenia and Severe Dysmyelopoiesis: Severe cytopenias of 2 or more peripheral blood myeloid cell lines (Hb < 10.0 gm with < 1% retics; absolute granulocyte count < 500/mm3 platelet count < 20,000/mm3) associated with dysmyelopoietic changes in the bone marrow.

• Severe Cytopenia and Clonal Chromosomal Abnormalities: Severe cytopenias of 2 or more myeloid cell lines associated with clonal, chromosomal abnormalities of the bone marrow.

• Myeloproliferative Diseases – (i.e. myelofibrosis, CMML)

• Juvenile myelomonocytic leukemia

• Chronic lymphocytic leukemia -- must have all three:

• Rai Stage III/IV

• Progression after previous CR or PR

• Recent chemotherapy responsiveness

• Advanced non-Hodgkin's (NHL).

• Low-grade NHL (working formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (> CR2, > PR2) or if no CR was achieved (> PR1).

• Mantle zone after initial therapy (> CR1, > PR1).

• Intermediate grade lymphoma (> PR2).

• High-grade NHL (IWF H, I, J) after initial therapy if > stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis.

• Recent chemotherapy responsiveness

• Advanced Hodgkin's disease beyond PR2 (> CR3, > PR3).

• Recent chemotherapy responsiveness

• Multiple Myeloma after initial therapy.

• Advanced (III) stage

• Beta 2 microglobulin > 6

• Donors and recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota.

Exclusion Criteria:

-

Trial Contact Information

Trial Lead Organizations/Sponsors

Daniel J. Weisdorf, MD

Daniel J. Weisdorf, MD

Principal Investigator

Daniel Weisdorf, M.D.		Ph: 612-624-3101
		Email: weisd001@umn.edu

U.S.A.
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Daniel Weisdorf, MD	Ph: 612-624-3101
			Email: weisd001@umn.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00176930
Information obtained from ClinicalTrials.gov on 2006-06-01

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