Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00322101
• Collaborator: National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 25
• Locations: 8
• Arms: 2
• Duration (Months): 105
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia.

PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes	Radiation: total-body irradiation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: cyclophosphamide; Drug: mycophenolate mofetil; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Procedure: peripheral blood stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Other: laboratory biomarker analysis; Genetic: cytogenetic analysis; Other: flow cytometry; Genetic: fluorescence in situ hybridization; Other: pharmacological study; Genetic: polymorphism analysis; Drug: tacrolimus; Drug: methotrexate	Phase 3

Detailed Description

OBJECTIVES:

1. Determine whether the conditioning intensity affects outcomes after HCT in patients with MDS or AML who have < 5% marrow myeloblasts at the time of HCT.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I (Nonmyeloablative regimen):

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

Arm II (Myeloablative regimen):

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (Nonmyeloablative regimen) CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	Radiation: total-body irradiation; Radiation; Other Names: TBI ; Drug: mycophenolate mofetil; Given orally; Other Names: Cellcept MMF ; Drug: cyclosporine; Given IV or orally; Other Names: ciclosporin cyclosporin cyclosporin A CYSP Sandimmune ; Drug: fludarabine phosphate; Given IV; Other Names: 2-F-ara-AMP Beneflur Fludara ; Procedure: peripheral blood stem cell transplantation; Undergo transplantation; Other Names: PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Undergo allogeneic transplantation; Other: laboratory biomarker analysis; Correlative studies; Genetic: cytogenetic analysis; Correlative studies; Other: flow cytometry; Correlative studies; Genetic: fluorescence in situ hybridization; Correlative studies; Other Names: fluorescence in situ hybridization (FISH) ; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies ; Genetic: polymorphism analysis; Correlative studies
Experimental: Arm II (Myeloablative regimen) CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.	Procedure: allogeneic hematopoietic stem cell transplantation; Undergo allogeneic transplantation; Drug: cyclophosphamide; Given IV; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: busulfan; Given IV or orally; Other Names: BSF BU Misulfan Mitosan Myeloleukon ; Drug: fludarabine phosphate; Given IV; Other Names: 2-F-ara-AMP Beneflur Fludara ; Procedure: peripheral blood stem cell transplantation; Undergo transplantation; Other Names: PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ; Other: laboratory biomarker analysis; Correlative studies; Other: flow cytometry; Correlative studies; Genetic: fluorescence in situ hybridization; Correlative studies; Other Names: fluorescence in situ hybridization (FISH) ; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies ; Genetic: polymorphism analysis; Correlative studies; Drug: tacrolimus; Given IV or orally; Other Names: FK 506 Prograf ; Drug: methotrexate; Given IV; Other Names: amethopterin Folex methylaminopterin Mexate MTX

Outcome Measures

Primary Outcome Measures

1. Overall Survival [At 2 years]

Secondary Outcome Measures

1. Progression-free Survival [After stem cell infusion to date of last follow up.]

   IWG criteria was used to determine disease progression

2. Non-relapse Mortality [At 100 days]

3. Donor Cell Engraftment [After stem cell infusion to day 28]

   Chimerism analysis was performed in patients who recieved nonmyeloablative tranplsnat. In this group the definition of engraftment was a CD3 count greater than 50%. In the myeloablative group, engraftment was defined as an absolute neutrophil count greater than 50%.

4. Incidence of Disease Progression/Relapse [After stem cell infusion to date of last follow up.]

   Disease progression/relapse was defined by IWG criteria

5. Incidence and Severity of Acute and Chronic Graft-vs-host Disease [After transplantation]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Myelodysplastic syndrome (MDS) or transformed acute myelogenous leukemia (transformed from MDS)

• De novo acute myelogenous leukemia (AML) beyond first remission

• Intermediate or high risk de novo AML in first complete response (at FHCRC unrelated donor recipients only)

• Chemotherapy required prior to HCT for all patients:

• 1. Interval between start of a cycle of cytoreductive chemotherapy and infusion of donor stem cells must be at least 30 days; chemotherapy received for disease maintenance will be allowed during this time period
• 1. All patients must have < 5% myeloblasts based on marrow morphology performed within 21 days prior to start of conditioning regimen and at least 3-4 weeks after the start of pre-transplant cytoreductive chemotherapy
• 1. All patients must have no circulating peripheral blood myeloblasts present based on morphologic analysis

• Age 65 years or under for patients with related donors; age 60 years or under for patients with unrelated donors

• HCT-Specific Comorbidity Index Score (HCT-CI) < 3

• Related donor (age > 12 years, nonsyngeneic) or unrelated donor, HLA phenotypically or genotypically identical at the allele level at A,B,C,DRQ1, and CBQ1

• DONOR: Related or unrelated donors who are genotypically or phenotypically matched by high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1); class 1 single allele mismatch allowed

• DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A0101 and the donor is A0201, and this type of mismatch is not allowed

• DONOR: A positive anti-donor cytotoxic crossmatch or flow cytometric assay is an absolute donor exclusion at FHCRC/SCCA

• DONOR: Age >= 12 years

• DONOR: Donors must consent to PBSC mobilization with G-CSF and leukaphereses; bone marrow as a source of stem cells will not be allowed

• DONOR: Donor must have adequate veins for leukaphereses or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

• HIV seropositivity

• Fungal infections with radiographic progression after appropriate therapy for greater than one month

• Organ dysfunction

• Symptomatic coronary artery disease or ejection fraction < 35%

• DLCO < 65%, FEV1 < 65% or receiving supplementary continuous oxygen

• Liver function abnormalities: Patients 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, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced 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 > 3 mg/dL, and symptomatic biliary disease will be excluded

• Karnofsky Performance Score < 70

• Lansky-Play Performance Score < 70 for pediatric patients

• Life expectancy severely limited (< 2 years) by disease other than MDS/AML

• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment

• Patients with active non-hematological malignancies except:

• 1. Patients with follicular or low grade lymphoma will be eligible as long as they have not and do not require active treatment for control of their disease
• 1. Patients with localized non-melanoma skin malignancies

• Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication

• Females who are pregnant or breastfeeding

• Patients with systemic, uncontrolled infections

• Active CNS disease as identified by positive CSF cytospin

• DONOR: Identical twin

• DONOR: Age < 12 years

• DONOR: Pregnancy

• DONOR: HIV seropositivity

• DONOR: Inability to achieve adequate venous access

• DONOR: Known adverse reaction to G-CSF

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HealthOne Presbyterian St. Lukes Medical Center	Denver	Colorado	United States
2	Emory University	Altanta	Georgia	United States	30322
3	Weill Cornell University	New York	New York	United States	10021
4	University of Utah	Salt Lake City	Utah	United States	84112
5	Veterans Administration Center-Seattle	Seattle	Washington	United States	98108
6	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
7	Medical College Wisconsin	Milwaukee	Wisconsin	United States
8	Technical University Dresden	Dresden	Saxony	Germany	01307

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Bart Scott, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00322101
• Other Study ID Numbers: 1992.00; NCI-2010-00737; P01CA078902; K23HL084054; P01CA018029; P01HL036444
• First Posted: May 4, 2006
• Last Update Posted: Oct 31, 2014
• Last Verified: Oct 1, 2014

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Recurrence; Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Busulfan; Methotrexate; Fludarabine; Fludarabine phosphate; Tacrolimus; Cyclosporins

Study Results

Participant Flow

Recruitment Details	Patients were recruited from medical clinics while being evaluated for stem cell transplantation

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Period Title: Overall Study
STARTED	14	11
COMPLETED	14	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)	Total
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.	Total of all reporting groups
Overall Participants	14	11	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	11 100%	25 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.47 (9.49)	52.82 (5.78)	52.2 (7.94)
Sex: Female, Male (Count of Participants)
Female	8 57.1%	3 27.3%	11 44%
Male	6 42.9%	8 72.7%	14 56%
Region of Enrollment (participants) [Number]
United States	8 57.1%	7 63.6%	15 60%
Germany	6 42.9%	4 36.4%	10 40%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

2 patients in the nonmyeloablative arm did not receive transplant due to relapse and withdrawal of consent

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	6 42.9%	6 54.5%

2. Secondary Outcome

Title	Progression-free Survival
Description	IWG criteria was used to determine disease progression
Time Frame	After stem cell infusion to date of last follow up.

Outcome Measure Data

Analysis Population Description

2 patients in the nonmyeloablative arm did not receive a transplant due to relapse and withdrawal of consent

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	7 50%	5 45.5%

3. Secondary Outcome

Title	Non-relapse Mortality
Time Frame	At 100 days

Outcome Measure Data

Analysis Population Description

2 patients in the nonmyeloablative arm did not receive transplant due to relapse and withdrawal of consent

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	Donor Cell Engraftment
Description	Chimerism analysis was performed in patients who recieved nonmyeloablative tranplsnat. In this group the definition of engraftment was a CD3 count greater than 50%. In the myeloablative group, engraftment was defined as an absolute neutrophil count greater than 50%.
Time Frame	After stem cell infusion to day 28

Outcome Measure Data

Analysis Population Description

2 patients who were randomized to receive nonmyeloablative conditioning did not undergo transplant due to relapse and withdrawal of consent

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	11 78.6%	11 100%

5. Secondary Outcome

Title	Incidence of Disease Progression/Relapse
Description	Disease progression/relapse was defined by IWG criteria
Time Frame	After stem cell infusion to date of last follow up.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	7 50%	2 18.2%

6. Secondary Outcome

Title	Incidence and Severity of Acute and Chronic Graft-vs-host Disease
Time Frame	After transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Nonmyeloablative Regimen)	Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.	CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Measure Participants	12	11
Number [participants]	1 7.1%	4 36.4%

Adverse Events

Arm/Group Title	Arm I (Nonmyeloablative Regimen)		Arm II (Myeloablative Regimen)
Arm/Group Description	CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.		CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
All Cause Mortality
	Arm I (Nonmyeloablative Regimen)		Arm II (Myeloablative Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Nonmyeloablative Regimen)		Arm II (Myeloablative Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		4/11 (36.4%)
Blood and lymphatic system disorders
Thrombotic Microangiopathy	0/12 (0%)	0	1/11 (9.1%)	1
Cardiac disorders
tachycardia and hypotenstion	1/12 (8.3%)	1	0/11 (0%)	0
Gastrointestinal disorders
severe diarrhea due to gut GVHD	2/12 (16.7%)	2	2/11 (18.2%)	2
Mucositis	0/12 (0%)	0	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Nonmyeloablative Regimen)		Arm II (Myeloablative Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		11/11 (100%)
Gastrointestinal disorders
Mucositis	0/12 (0%)	0	6/11 (54.5%)	6
Infections and infestations
Infection	12/12 (100%)	12	5/11 (45.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.