Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes

• Sponsor: Eastern Cooperative Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00045305
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 17
• Locations: 6
• Arm: 1
• Duration (Months): 112
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system 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 pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms	Drug: Cyclosporine; Drug: Methotrexate; Drug: Photopheresis; Drug: Mycofenolate mofetil; Drug: Pentostatin; Procedure: allogeneic bone marrow; Procedure: peripheral blood stem cell; Radiation: Total body irradiation	Phase 2

Detailed Description

OBJECTIVES:

• Determine the complete response rate in patients with myelodysplastic syndromes treated with reduced-intensity allogeneic bone marrow transplantation, including photopheresis, total body irradiation, and pentostatin.

• Determine the disease-free and overall survival of patients treated with this regimen.

• Determine the engraftment rate of donor cells in patients treated with this regimen.

• Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a single-arm, two-stage, multicenter phase II study.

• Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6 and receive pentostatin intravenously (IV )continuously on days -5 and -4. Total body irradiation is administered on days -3 and -2 for a total of 3 doses.

• Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on day 0.

• Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also receive methotrexate IV on days 1 and 3.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 33 patients would be accrued for this study within 2.1 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm I Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.

Drug: Cyclosporine; Immunosuppressant; Other Names: Sandimmune® cyclosporin A Neoral®Gengraf® Gengraf® CSA ; Drug: Methotrexate; Antimetabolite; Other Names: Methotrexate sodium MTX Mexate Mexate-AQ Folex Folex PFS Abitrexate Rheumatrex Amethopterin ; Drug: Photopheresis; Psoralens; Other Names: 8-methoxypsoralen Uvadex ® Methoxsalen ; Drug: Mycofenolate mofetil; an antibiotic with immunosuppressamt properties isolated from Penicillium spp; Other Names: Cellcept® RS-61443 mycophenolic acid Lilly-68618 MMF Mycophenolate mofetil ; Drug: Pentostatin; Purine analogue; Other Names: DCF 2-Deoxycoformycin Nipent ; Procedure: allogeneic bone marrow; Unmanipulated allogeneic bone marrow; Procedure: peripheral blood stem cell; G-CSF mobilized peripheral blood stem cell; Radiation: Total body irradiation; a total of 600 cGy given in 3 200 cGy fractionated doses; Other Names: radiation therapy

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.]

   Completed response is defined as: Bone marrow evaluation: Repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation). Peripheral blood evaluation [absolute values must last at least 2 months] Hemoglobin >11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present

Secondary Outcome Measures

1. Number of Patients Who Developed Disease Progression After Achieving Complete Response [Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.]

   Disease free survival (DFS) was listed as a secondary endpoint in the study protocol, which would be assessed in patients who achieved complete response (CR). It was defined to be time from CR to documented progression or to death without progression. Patients without documented progression or death reported were censored at the time of last disease evaluation. However, due to the small number of patients with CR, the number of patients who developed disease progression was reported here.

2. Overall Survival [Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.]

   Overall survival (OS) is defined to be the time from registration to death from any cause, with follow-up censored at the date of last contact. Kaplan-Meier method was used to estimate the distribution of OS.

3. Proportion of Graft Versus Host Disease [Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.]

   Proportion of Graft versus Host Disease is calculated as number of patients with Graft versus Host Disease divided by all eligible and treated patients

4. Time to Engraftment for Neutrophil [Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.]

   Time to neutrophil engraftment is defined from date of infusion to date of neutrophil engraftment. Neutrophil engraftment is defined as ANC > 500/mm3 on two consecutive measurements. The date of engraftment is the date of the first ANC > 500/mm3.

5. Time to Engraftment for Platelet [Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.]

   Time to platelet engraftment is defined from date of infusion to date of platelet engraftment. The platelet engraftment is defined as platelets > 20,000 on two consecutive measurements, at least seven days apart, without platelet transfusions in between and for at least three days before the first measurement that is over 20,000. The date of engraftment is the date of the first measurement that is over 20,000.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• One of the following cytologically proven myelodysplastic syndromes

• Refractory anemia (RA)

• RA with ringed sideroblasts

• RA with excess blasts

• Chronic myelomonocytic leukemia

• International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell transfusion dependence for at least 6 months (2 units per month)

• Patients with an IPSS score less than 0.5 may be eligible provided they previously had a higher IPSS score and received chemotherapy at that time

• Suitable human leukocyte antigen (HLA)-matched donor (related or unrelated) available

• No cord blood donors

• Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci and may be a sibling, parent, or child

• Unrelated donors must have high resolution typing done at A, B, C and DR, and must be matched at all or may have a single antigen or allele mismatch at no more than one of these loci

• Patients must have < 20% blasts on bone marrow study within 1 month of study entry

• Age of 18 to 70 years

• Eastern Cooperative Oncology Group performance status 0-1

• Life expectancy at least 6 months

• At least 90 days since prior autologous bone marrow transplantation

• Serum erythropoietin level greater than 100 for patients who have not received a prior course of epoetin alfa

• No iron deficiency

• Iron deficiency anemia treated with iron replacement therapy allowed

• Bilirubin less than 2.0 mg/dL

• Alkaline phosphatase less than 2 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times ULN

• Creatinine less than 2.0 mg/dL OR creatinine clearance greater than 50 mL/min

• Left ventricular ejection fraction (LVEF) at least 45% by Multigated Acquisition scan (MUGA) or echocardiogram

• Carbon Monoxide Diffusing Capacity (DLCO) at least 50% of predicted (corrected for hemoglobin)

• Forced expiratory volume in 1 second (FEV_1) at least 50% of predicted

• Recovered from prior chemotherapy

• Physically and psychologically capable of undergoing study regimen

• Able to receive 600 cGy of total body irradiation

• HIV negative

• Negative pregnancy test

Exclusion Criteria:

• Pregnant or nursing

• Having other medical condition that would reduce life expectancy

• Active ongoing infection

• Prior myeloablative or nonmyeloablative allogeneic transplantation for Myelodysplastic syndrome or acute myeloid leukemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Tufts-NEMC Cancer Center	Boston	Massachusetts	United States	02111
4	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
5	Jewish Hospital Cancer Center	Cincinnati	Ohio	United States	45236
6	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283

Sponsors and Collaborators

• Eastern Cooperative Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Selina M. Luger, MD, Abramson Cancer Center of the University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00045305
• Other Study ID Numbers: CDR0000256928; E1902; U10CA021115
• First Posted: Jan 27, 2003
• Last Update Posted: Jan 19, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Eastern Cooperative Oncology Group: chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable
• Additional relevant MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Cyclosporine; Mycophenolic Acid; Methotrexate; Pentostatin; Methoxsalen; Cyclosporins

Study Results

Participant Flow

Recruitment Details	This trial was open to accrual on May 18, 2005. By September 23, 2009, 17 patients were enrolled to the trial and the first 15 patients were included in the interim analysis. This trial did not meet pre-defined criteria to continue to the second stage. In the end, a total of 17 patients were enrolled to the trial from 7 participating institutions.

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
Period Title: Overall Study
STARTED	17
Eligible and Treated	17
COMPLETED	3
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	5 29.4%
Male	12 70.6%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	Completed response is defined as: Bone marrow evaluation: Repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation). Peripheral blood evaluation [absolute values must last at least 2 months] Hemoglobin >11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present
Time Frame	Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	17
Number (90% Confidence Interval) [percentage of participants]	35.3 207.6%

2. Secondary Outcome

Title	Number of Patients Who Developed Disease Progression After Achieving Complete Response
Description	Disease free survival (DFS) was listed as a secondary endpoint in the study protocol, which would be assessed in patients who achieved complete response (CR). It was defined to be time from CR to documented progression or to death without progression. Patients without documented progression or death reported were censored at the time of last disease evaluation. However, due to the small number of patients with CR, the number of patients who developed disease progression was reported here.
Time Frame	Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Outcome Measure Data

Analysis Population Description

eligible and treated patients who achieved complete response

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	6
Number [participants]	1 5.9%

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) is defined to be the time from registration to death from any cause, with follow-up censored at the date of last contact. Kaplan-Meier method was used to estimate the distribution of OS.
Time Frame	Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	17
Median (95% Confidence Interval) [years]	1.2

4. Secondary Outcome

Title	Proportion of Graft Versus Host Disease
Description	Proportion of Graft versus Host Disease is calculated as number of patients with Graft versus Host Disease divided by all eligible and treated patients
Time Frame	Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	17
Number (95% Confidence Interval) [proportion of participants]	0.412 2.4%

5. Secondary Outcome

Title	Time to Engraftment for Neutrophil
Description	Time to neutrophil engraftment is defined from date of infusion to date of neutrophil engraftment. Neutrophil engraftment is defined as ANC > 500/mm3 on two consecutive measurements. The date of engraftment is the date of the first ANC > 500/mm3.
Time Frame	Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	17
Median (95% Confidence Interval) [days]	18

6. Secondary Outcome

Title	Time to Engraftment for Platelet
Description	Time to platelet engraftment is defined from date of infusion to date of platelet engraftment. The platelet engraftment is defined as platelets > 20,000 on two consecutive measurements, at least seven days apart, without platelet transfusions in between and for at least three days before the first measurement that is over 20,000. The date of engraftment is the date of the first measurement that is over 20,000.
Time Frame	Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD. Cyclosporine: Immunosuppressant Methotrexate: Antimetabolite
Measure Participants	17
Median (95% Confidence Interval) [days]	18

Adverse Events

Time Frame	Assessed at 30 days, 50 days, 100 days and 1 year post transplant
Adverse Event Reporting Description	Any severe (Grade ≥ 3) long term toxicity that the patient has experienced prior to diagnosis of progression/relapse that has not been previously reported would be collected via long-term follow up form at the following schedule: every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5
Arm/Group Title	Arm I
Arm/Group Description	Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	14/17 (82.4%)
Febrile neutropenia	6/17 (35.3%)
Cardiac disorders
Heart failure	1/17 (5.9%)
Cardiac disorders - Other, specify	1/17 (5.9%)
Eye disorders
Eye disorders - Other, specify	1/17 (5.9%)
Gastrointestinal disorders
Diarrhea	4/17 (23.5%)
Mucositis oral	1/17 (5.9%)
Nausea	3/17 (17.6%)
Vomiting	1/17 (5.9%)
Abdominal pain	2/17 (11.8%)
General disorders
Fatigue	4/17 (23.5%)
Edema limbs	2/17 (11.8%)
Hepatobiliary disorders
Hepatic failure	3/17 (17.6%)
Infections and infestations
Enterocolitis infectious	1/17 (5.9%)
Infections and infestations - Other, spe	1/17 (5.9%)
Bladder infection	2/17 (11.8%)
Upper respiratory infection	1/17 (5.9%)
Urinary tract infection	1/17 (5.9%)
Infections and infestations - Other, spe	4/17 (23.5%)
Investigations
White blood cell decreased	17/17 (100%)
Neutrophil count decreased	17/17 (100%)
Platelet count decreased	17/17 (100%)
Alkaline phosphatase increased	2/17 (11.8%)
Alanine aminotransferase increased	3/17 (17.6%)
Aspartate aminotransferase increased	2/17 (11.8%)
Blood bilirubin increased	6/17 (35.3%)
Creatinine increased	2/17 (11.8%)
Metabolism and nutrition disorders
Iron overload	1/17 (5.9%)
Anorexia	1/17 (5.9%)
Dehydration	1/17 (5.9%)
Hyperglycemia	1/17 (5.9%)
Hyperkalemia	1/17 (5.9%)
Hypokalemia	1/17 (5.9%)
Hyponatremia	1/17 (5.9%)
Nervous system disorders
Peripheral sensory neuropathy	1/17 (5.9%)
Psychiatric disorders
Confusion	1/17 (5.9%)
Renal and urinary disorders
Acute kidney injury	4/17 (23.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/17 (5.9%)
Hypoxia	1/17 (5.9%)
Pneumothorax	1/17 (5.9%)
Respiratory, thoracic and mediastinal di	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/17 (5.9%)
Vascular disorders
Vascular disorders - Other, specify	1/17 (5.9%)
Thromboembolic event	1/17 (5.9%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	17/17 (100%)
Cardiac disorders
Sinus bradycardia	1/17 (5.9%)
Sinus tachycardia	2/17 (11.8%)
Acute coronary syndrome	1/17 (5.9%)
Pericardial effusion	1/17 (5.9%)
Ear and labyrinth disorders
External ear inflammation	1/17 (5.9%)
Endocrine disorders
Cushingoid	1/17 (5.9%)
Eye disorders
Dry eye	1/17 (5.9%)
Conjunctivitis	1/17 (5.9%)
Blurred vision	1/17 (5.9%)
Gastrointestinal disorders
Colitis	2/17 (11.8%)
Constipation	3/17 (17.6%)
Diarrhea	13/17 (76.5%)
Abdominal distension	1/17 (5.9%)
Dry mouth	1/17 (5.9%)
Dysphagia	1/17 (5.9%)
Esophagitis	3/17 (17.6%)
Gastritis	1/17 (5.9%)
Hemorrhoids	1/17 (5.9%)
Mucositis oral	2/17 (11.8%)
Mucositis oral	1/17 (5.9%)
Nausea	15/17 (88.2%)
Vomiting	11/17 (64.7%)
Abdominal pain	6/17 (35.3%)
General disorders
Fatigue	14/17 (82.4%)
Fever	5/17 (29.4%)
Chills	1/17 (5.9%)
Injection site reaction	2/17 (11.8%)
Edema limbs	12/17 (70.6%)
Edema trunk	1/17 (5.9%)
General disorders and administration sit	1/17 (5.9%)
Infections and infestations
Enterocolitis infectious	1/17 (5.9%)
Infections and infestations - Other, spe	1/17 (5.9%)
Urinary tract infection	1/17 (5.9%)
Injury, poisoning and procedural complications
Fracture	1/17 (5.9%)
Investigations
White blood cell decreased	17/17 (100%)
Neutrophil count decreased	17/17 (100%)
Platelet count decreased	16/17 (94.1%)
Electrocardiogram QT corrected interval	1/17 (5.9%)
Weight loss	3/17 (17.6%)
Alkaline phosphatase increased	13/17 (76.5%)
Alanine aminotransferase increased	12/17 (70.6%)
Aspartate aminotransferase increased	13/17 (76.5%)
Blood bilirubin increased	17/17 (100%)
Creatinine increased	16/17 (94.1%)
Metabolism and nutrition disorders
Anorexia	7/17 (41.2%)
Dehydration	2/17 (11.8%)
Hypoglycemia	1/17 (5.9%)
Hypomagnesemia	2/17 (11.8%)
Hyperkalemia	1/17 (5.9%)
Hypokalemia	1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	2/17 (11.8%)
Generalized muscle weakness	1/17 (5.9%)
Chest wall pain	1/17 (5.9%)
Pain in extremity	1/17 (5.9%)
Myalgia	1/17 (5.9%)
Nervous system disorders
Dysgeusia	4/17 (23.5%)
Dizziness	3/17 (17.6%)
Peripheral sensory neuropathy	3/17 (17.6%)
Tremor	1/17 (5.9%)
Headache	6/17 (35.3%)
Sinus pain	1/17 (5.9%)
Psychiatric disorders
Insomnia	4/17 (23.5%)
Confusion	1/17 (5.9%)
Anxiety	1/17 (5.9%)
Depression	1/17 (5.9%)
Renal and urinary disorders
Hematuria	1/17 (5.9%)
Urinary frequency	1/17 (5.9%)
Reproductive system and breast disorders
Vaginal pain	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/17 (11.8%)
Cough	1/17 (5.9%)
Dyspnea	7/17 (41.2%)
Hiccups	1/17 (5.9%)
Pleural effusion	1/17 (5.9%)
Pneumonitis	1/17 (5.9%)
Respiratory, thoracic and mediastinal di	1/17 (5.9%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	2/17 (11.8%)
Dry skin	2/17 (11.8%)
Alopecia	4/17 (23.5%)
Pruritus	3/17 (17.6%)
Rash maculo-papular	12/17 (70.6%)
Erythema multiforme	1/17 (5.9%)
Purpura	1/17 (5.9%)
Vascular disorders
Hypertension	3/17 (17.6%)
Hypotension	3/17 (17.6%)
Hot flashes	1/17 (5.9%)
Thromboembolic event	1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.