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Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

Primary Purpose

Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
alemtuzumab
total-body irradiation
fludarabine phosphate
cyclosporine
mycophenolate mofetil
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
graft versus host disease prophylaxis/therapy
laboratory biomarker analysis
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Undifferentiated Leukemia

Eligibility Criteria

undefined - 74 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The patient must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy Patients with hematologic malignancies treatable with HCT will be included: Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B-cell NHL: not eligible for autologous HCT, not eligible for conventional myeloablative HCT, or after failed autologous HCT; Low grade NHL: with < 6 month duration of complete response (CR) between courses of conventional therapy; Mantle cell NHL: may be treated in first CR; Chronic lymphocytic leukemia (CLL): must have failed 2 lines of conventional therapy and must be refractory to fludarabine; this includes patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog] or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine [or another nucleoside analog); Hodgkin's disease (HD): must have received and failed frontline therapy and have failed or were not eligible for autologous transplant; Multiple myeloma (MM): must have received prior chemotherapy or failed autografting; following a planned autologous transplant [tandem] is allowed; Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of transplant; Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of transplant; Chronic myelogenous leukemia (CML): patients will be accepted beyond first clinical progression (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant; Myelodysplastic syndrome/myeloproliferative disease (MDS/MPD): must have failed previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant; Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy Patient refuses to be treated on a conventional transplant protocol; for this inclusion criteria, transplants must be approved by both the participating institution's patient review committee, such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC), and the FHCRC principal investigator Patient with related or unrelated donors for whom: There is a likelihood of disease progression while HLA typing and results of a preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found; Patient and donor must be matched for at least one DRB1 allele and one DQB1 allele; Best available matches are HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch; There is no indication for an autologous transplantation as a treatment option DONOR: For HLA matching inclusion criteria, see patient inclusion criteria DONOR: Only peripheral blood stem cells (PBSC) will be permitted as a HSC source on this protocol Exclusion Criteria: Positive crossmatch between donor and recipients Patient's life expectancy is severely limited by diseases other than malignancy Patient has central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML Patient is a fertile man or woman unwilling to use contraceptives during and for up to 12 months post treatment Patient is a female who is pregnant or breastfeeding Patient is human immunodeficiency virus (HIV) positive Patients with active non-hematologic malignancies (except non-melanoma skin cancers) Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence Patient has a fungal infection with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month Patient has the following organ dysfunction: Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if age > 50 years or if the patient has a history of anthracyclines or history of cardiac disease; Diffusion capacity of the lung for carbon monoxide (DLCO) < 35% total lung capacity (TLC) < 35%, forced expiratory volume of the lung in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen; the FHCRC study principal investigator (PI) must approve enrollment of all patients with pulmonary nodules; Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease Patient has poorly controlled hypertension and on multiple antihypertensives Karnofsky performance score < 70 for adult patients Lansky play-performance score < 70 for pediatric patients Patient received cytotoxic agents for "cytoreduction" within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning; (exceptions are hydroxyurea and imatinib mesylate) DONOR: Marrow donors DONOR: Positive crossmatch between donor and recipient DONOR: Donor is HIV-positive and/or has a medical condition that would result in increased risk for filgrastim (G-CSF) mobilization and harvest of PBSC DONOR: Donor age < 12 years

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • University of Torino

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, TBI, transplant)

Arm Description

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab IV over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose TBI on day 0. ALLOGENEIC PBSCT: After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD.

Outcomes

Primary Outcome Measures

Incidence of Grade III-IV Acute GVHD
Severity of Individual Organ Involvement Liver: Stage 2 - bilirubin (3-5.9mg/100ml) Stage 3 - bilirubin (6-14.9mg/100ml) Stage 4 - bilirubin > 15mg/100ml Gut: Diarrhea is graded stage 1 to stage 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as stage 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall Severity of GVHD Grade III - Stage 2 to 4 gastrointestinal involvement and/or Stage 2 to 4 liver involvement with or without a rash Grade IV - Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Secondary Outcome Measures

Incidence of Graft Rejection
Percentage patients that experienced graft rejection.
Incidence of High-dose Corticosteroid Utilization.
Percentage patients requiring steroids greater than 1 mg/kg.
Incidence of Non-relapse Mortality
Percentage patient deaths due to non-relapse mortality
Incidence of Infection
Percentage patients that experienced infection(s).
Immune Reconstitution
The outcome of immune reconstitution was not analyzed by the collaborating laboratory because only a small number of patients were only enrolled in Dose Level 1 (no alemtuzumab). The Dose Level 1 patients were going to be the baseline for which to compare the other patients on Dose Level 2 (and 3) who would have received alemtuzumab. The collaborating investigator determined that the study was not worthwhile performing based on this information.
Disease Progression/Relapse
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%. AML, ALL >5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease. CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.

Full Information

First Posted
July 8, 2005
Last Updated
April 25, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00118352
Brief Title
Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Official Title
Campath (Alemtuzumab) Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class II Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies: A Multicenter Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
May 26, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial is studying the side effects and best dose of alemtuzumab when given together with fludarabine phosphate and total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients who are undergoing a donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, a monoclonal antibody, such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
Detailed Description
PRIMARY OBJECTIVES: I. To determine which dose of Campath (alemtuzumab) allows related and unrelated human leukocyte antigen (HLA) class-II mismatched hematopoietic cell transplantation (HCT) with an incidence of grade III-IV acute graft-versus-host disease (GVHD) less than 40%. SECONDARY OBJECTIVES: I. Incidence of graft rejection. II. Number of days of steroids >= 1mg/kg required before day 100 in each patient. III. Incidence of non-relapse mortality. IV. Risk/incidence of infections. V. Immune reconstitution. VI. Risk for disease progression and relapse. OUTLINE: This is a dose-escalation study of alemtuzumab. NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0. ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD. After completion of study treatment, patients are followed up periodically for 12 months, at 18 months, and then annually for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Myelomonocytic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Juvenile Myelomonocytic Leukemia, Mast Cell Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, TBI, transplant)
Arm Type
Experimental
Arm Description
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab IV over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose TBI on day 0. ALLOGENEIC PBSCT: After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD.
Intervention Type
Biological
Intervention Name(s)
alemtuzumab
Other Intervention Name(s)
anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H, Monoclonal Antibody CD52
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Undergo low-dose TBI
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given PO or IV
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo allogeneic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo PBSCT
Intervention Type
Biological
Intervention Name(s)
graft versus host disease prophylaxis/therapy
Other Intervention Name(s)
prophylaxis/therapy, graft versus host disease, prophylaxis/therapy, GVHD
Intervention Description
Undergo GVHD prophylaxis/therapy
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Incidence of Grade III-IV Acute GVHD
Description
Severity of Individual Organ Involvement Liver: Stage 2 - bilirubin (3-5.9mg/100ml) Stage 3 - bilirubin (6-14.9mg/100ml) Stage 4 - bilirubin > 15mg/100ml Gut: Diarrhea is graded stage 1 to stage 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as stage 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall Severity of GVHD Grade III - Stage 2 to 4 gastrointestinal involvement and/or Stage 2 to 4 liver involvement with or without a rash Grade IV - Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time Frame
100 days after transplant
Secondary Outcome Measure Information:
Title
Incidence of Graft Rejection
Description
Percentage patients that experienced graft rejection.
Time Frame
84 days after transplant
Title
Incidence of High-dose Corticosteroid Utilization.
Description
Percentage patients requiring steroids greater than 1 mg/kg.
Time Frame
100 days after transplant
Title
Incidence of Non-relapse Mortality
Description
Percentage patient deaths due to non-relapse mortality
Time Frame
100 days after transplant
Title
Incidence of Infection
Description
Percentage patients that experienced infection(s).
Time Frame
Up to 5 years post-transplant
Title
Immune Reconstitution
Description
The outcome of immune reconstitution was not analyzed by the collaborating laboratory because only a small number of patients were only enrolled in Dose Level 1 (no alemtuzumab). The Dose Level 1 patients were going to be the baseline for which to compare the other patients on Dose Level 2 (and 3) who would have received alemtuzumab. The collaborating investigator determined that the study was not worthwhile performing based on this information.
Time Frame
Up to 1 year post-transplant
Title
Disease Progression/Relapse
Description
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%. AML, ALL >5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease. CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy Patients with hematologic malignancies treatable with HCT will be included: Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B-cell NHL: not eligible for autologous HCT, not eligible for conventional myeloablative HCT, or after failed autologous HCT; Low grade NHL: with < 6 month duration of complete response (CR) between courses of conventional therapy; Mantle cell NHL: may be treated in first CR; Chronic lymphocytic leukemia (CLL): must have failed 2 lines of conventional therapy and must be refractory to fludarabine; this includes patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog] or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine [or another nucleoside analog); Hodgkin's disease (HD): must have received and failed frontline therapy and have failed or were not eligible for autologous transplant; Multiple myeloma (MM): must have received prior chemotherapy or failed autografting; following a planned autologous transplant [tandem] is allowed; Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of transplant; Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of transplant; Chronic myelogenous leukemia (CML): patients will be accepted beyond first clinical progression (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant; Myelodysplastic syndrome/myeloproliferative disease (MDS/MPD): must have failed previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant; Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy Patient refuses to be treated on a conventional transplant protocol; for this inclusion criteria, transplants must be approved by both the participating institution's patient review committee, such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC), and the FHCRC principal investigator Patient with related or unrelated donors for whom: There is a likelihood of disease progression while HLA typing and results of a preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found; Patient and donor must be matched for at least one DRB1 allele and one DQB1 allele; Best available matches are HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch; There is no indication for an autologous transplantation as a treatment option DONOR: For HLA matching inclusion criteria, see patient inclusion criteria DONOR: Only peripheral blood stem cells (PBSC) will be permitted as a HSC source on this protocol Exclusion Criteria: Positive crossmatch between donor and recipients Patient's life expectancy is severely limited by diseases other than malignancy Patient has central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML Patient is a fertile man or woman unwilling to use contraceptives during and for up to 12 months post treatment Patient is a female who is pregnant or breastfeeding Patient is human immunodeficiency virus (HIV) positive Patients with active non-hematologic malignancies (except non-melanoma skin cancers) Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence Patient has a fungal infection with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month Patient has the following organ dysfunction: Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if age > 50 years or if the patient has a history of anthracyclines or history of cardiac disease; Diffusion capacity of the lung for carbon monoxide (DLCO) < 35% total lung capacity (TLC) < 35%, forced expiratory volume of the lung in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen; the FHCRC study principal investigator (PI) must approve enrollment of all patients with pulmonary nodules; Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease Patient has poorly controlled hypertension and on multiple antihypertensives Karnofsky performance score < 70 for adult patients Lansky play-performance score < 70 for pediatric patients Patient received cytotoxic agents for "cytoreduction" within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning; (exceptions are hydroxyurea and imatinib mesylate) DONOR: Marrow donors DONOR: Positive crossmatch between donor and recipient DONOR: Donor is HIV-positive and/or has a medical condition that would result in increased risk for filgrastim (G-CSF) mobilization and harvest of PBSC DONOR: Donor age < 12 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda Sandmaier
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

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