Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00060424
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 21
• Locations: 3
• Arm: 1
• Duration (Months): 90.7
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system from rejecting the donor's 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 before and after the transplant may stop this from happening.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia	Drug: Cyclosporine; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

1. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.

2. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

3. To characterize the rate and types of infections with this regimen.

4. To estimate the rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - A Multi-center Trial
• Study Start Date: Mar 1, 2003
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 22, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor, transplant, GVHD prophylaxis) NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

Drug: Cyclosporine; Given PO; Other Names: 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Neoral OL 27-400 Sandimmun Sandimmune SangCya ; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara Oforta SH T 586 ; Procedure: Hematopoietic Cell Transplantation; Undergo allogeneic peripheral blood stem cell transplant; Other Names: HCT Hematopoietic Stem Cell Transplantation HSCT stem cell transplantation ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Mycophenolate Mofetil; Given PO; Other Names: Cellcept MMF ; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic peripheral blood stem cell transplant; Other Names: Non-myeloablative allogeneic transplant Nonmyeloablative Stem Cell Transplantation NST ; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation

Outcome Measures

Primary Outcome Measures

1. Overall Survival [At 18 months]

   Number of patients surviving 18 months post-transplant.

Secondary Outcome Measures

1. Rate of Relapse [18 months]

   Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation.

2. Acute Grade II-IV GVHD and Chronic (Extensive) GVHD [aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.]

   Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 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. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

3. Rate and Types of Infections [18 months]

   Number of infections patients experienced, by infection type.

4. Transplant-related Mortality [At 200 days]

   Defined as death before day +200 not related to progression of disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL

• Patients with B-Cell CLL or PLL who have at least one of the following:

• Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)

• Failed FCR combination chemotherapy at any time point

• Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in first (1st) complete response (CR)

• Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is willing to undergo leukapheresis initially for collection of PBSC and subsequently for collection of peripheral blood mononuclear cells (PBMC) with filgrastim (G-CSF) mobilization and willing to donate stem cells

• DONOR: Related donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1

• DONOR: Donor must consent to G-CSF administration and leukapheresis

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

Exclusion Criteria:

• Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-1, or HTLV-2

• Active central nervous system (CNS) involvement with CLL

• 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

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

• Pregnant or breastfeeding women

• Karnofsky score =< 70

• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month

• Cytotoxic agents for "cytoreduction" (with the exception of imatinib mesylate [Gleevec], cytokine therapy, hydroxyurea, chlorambucil or Rituxan) within three weeks of the initiation of conditioning

• Active bacterial or fungal infections unresponsive to medical therapy

• Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled hypertension despite multiple antihypertensives

• Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring continuous supplementary oxygen, or severe deficits in pulmonary function testing as defined by pulmonary consultant service

• Liver function abnormalities: patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are 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

• DONOR: Age < 12 years

• DONOR: Identical twin

• DONOR: Pregnancy

• DONOR: Infection with HIV

• DONOR: Inability to achieve adequate venous access

• DONOR: Known allergy to filgrastim (G-CSF)

• DONOR: Current serious systemic illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Administration Center-Seattle	Seattle	Washington	United States	98108
2	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
3	University of Torino	Torino		Italy	10126

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Maloney, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Maloney, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00060424
• Other Study ID Numbers: 1711.00; NCI-2010-01276; NCI-2011-01116; 1711.00; P30CA015704
• First Posted: May 7, 2003
• Last Update Posted: Dec 8, 2017
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Leukemia, Prolymphocytic, B-Cell; Recurrence; Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 95.2%
>=65 years	1 4.8%
Sex: Female, Male (Count of Participants)
Female	5 23.8%
Male	16 76.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	18 85.7%
Unknown or Not Reported	3 14.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 95.2%
More than one race	0 0%
Unknown or Not Reported	1 4.8%
Region of Enrollment (participants) [Number]
United States	20 95.2%
Italy	1 4.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Number of patients surviving 18 months post-transplant.
Time Frame	At 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Measure Participants	21
Count of Participants [Participants]	15 71.4%

2. Secondary Outcome

Title	Rate of Relapse
Description	Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Measure Participants	21
Count of Participants [Participants]	8 38.1%

3. Secondary Outcome

Title	Acute Grade II-IV GVHD and Chronic (Extensive) GVHD
Description	Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 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. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time Frame	aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Measure Participants	21
Acute GVHD	10 47.6%
Chronic extensive GVHD	10 47.6%

4. Secondary Outcome

Title	Rate and Types of Infections
Description	Number of infections patients experienced, by infection type.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Measure Participants	21
Viral	27
Fungal	13
Fever of unknown origin	6
Bacterial	53
Other	5

5. Secondary Outcome

Title	Transplant-related Mortality
Description	Defined as death before day +200 not related to progression of disease.
Time Frame	At 200 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
Measure Participants	21
Count of Participants [Participants]	2 9.5%

Adverse Events

Time Frame	AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Arm/Group Title	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
Arm/Group Description	NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI
All Cause Mortality
	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
	Affected / at Risk (%)	# Events
Total	7/21 (33.3%)
Cardiac disorders
Cardiac Arrhythmia and Seizure	1/21 (4.8%)	1
Gastrointestinal disorders
Severe abnormal pain due to gut GVH	1/21 (4.8%)	1
Perforated sigmoid diverticulitis	1/21 (4.8%)	1
Immune system disorders
Death following progression of GVHD	1/21 (4.8%)	1
Death following disease progression post transplant	2/21 (9.5%)	2
Renal and urinary disorders
Death: Sepsis/Renal failure/ with history of GVHD	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Embolism	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)
	Affected / at Risk (%)	# Events
Total	15/21 (71.4%)
Blood and lymphatic system disorders
Neutropenia	10/21 (47.6%)	10
Thrombocytopenia	2/21 (9.5%)	2
Tumor lysis syndrome	1/21 (4.8%)	1
Cardiac disorders
Acute Pulmonary Embolism	1/21 (4.8%)	1
Hypotension	1/21 (4.8%)	1
Gastrointestinal disorders
Typhlitis & Bowel Perforation	1/21 (4.8%)	1
Hepatobiliary disorders
Hyperbilirubinemia	2/21 (9.5%)	2
Nervous system disorders
Neurotoxicity	1/21 (4.8%)	1
Renal and urinary disorders
Minimal hydronephosis	1/21 (4.8%)	1
Increased creatinine	1/21 (4.8%)	1
Renal failure	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/21 (9.5%)	2
Surgical and medical procedures
Cholecystectomy	1/21 (4.8%)	1

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.