Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00566696
• Collaborator: (none)
• Enrollment: 73
• Location: 1
• Arm: 1
• Actual Duration (Months): 145.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.

Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.

For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.

The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Acute Lymphocytic (ALL); Leukemia, Myeloid, Acute(AML); Leukemia, Myeloid, Chronic(CML); Juvenile Myelomonocytic Leukemia (JMML); Hemoglobinuria, Paroxysmal Nocturnal (PNH); Hodgkin Lymphoma; Lymphoma, Non-Hodgkin (NHL); Myelodysplastic Syndrome (MDS)	Device: CliniMACS; Procedure: Stem cell transplantation; Drug: Fludarabine; Drug: Thioplex®; Drug: L-phenylalanine mustard; Drug: Mycophenolate mofetil; Drug: Rituxan™; Drug: Alemtuzumab; Drug: Cyclophosphamide; Drug: Anti-thymocyte globulin (Rabbit); Drug: G-CSF; Drug: Muromonab	Phase 2

Detailed Description

This study will explore the following objectives:

1. To assess if the event-free survival at one-year post-transplant for research participants with high-risk hematologic malignancies can be improved following HAPLO hematopoietic stem cell transplant (HSCT) using a graft depleted of CD3+ cells ex vivo and a reduced intensity-conditioning regimen.

Secondary objectives:

1. To estimate the one-year overall survival (OS) and disease-free survival (DFS) for research participants who receive this study treatment.

2. To estimate the cumulative incidence of relapse for research participants who receive this study treatment.

3. To estimate the rate of overall grade III-IV acute GVHD, and the rate and severity of chronic GVHD in research participants.

4. To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant.

Exploratory objectives:

1. To explore the biologic significance of soluble interleukin-2 receptor and immunologic state [quantitative lymphocyte studies, V beta spectratyping, T-cell receptor excision circles (TREC) assay] to predict the development of acute and chronic GVHD in these research participants.

2. To measure the pharmacokinetics of Campath-1H in pediatric HAPLO HSCT recipients

NOTE: This protocol originally used muromonab (OKT3) in the conditioning regimen to prepare participants for haploidentical HCT. After muromonab became unavailable from the manufacturer in 2010, muromonab was replaced by alemtuzumab (Campath-1H) for use in subsequent participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Reduced Intensity Conditioning Regimen With CD3-Depleted Hematopoietic Stem Cells to Improve Survival for Patients With Hematologic Malignancies Undergoing Haploidentical Stem Cell Transplantation
• Actual Study Start Date: Dec 14, 2007
• Actual Primary Completion Date: Jan 27, 2016
• Actual Study Completion Date: Feb 6, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: High-Risk Hematologic Malignancies Participants meeting eligibility criteria undergo haploidentical stem cell transplantation along with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (after January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF. Grafts from suitable haploidentical donors are processed using the CliniMACS system.

Device: CliniMACS; Miltenyi Biotec CliniMACS stem cell selection device; Procedure: Stem cell transplantation; An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.; Drug: Fludarabine; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Fludara ; Drug: Thioplex®; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Thiotepa TESPA TSPA ; Drug: L-phenylalanine mustard; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Melphalan Phenylalanine mustard L-PAM L-sarcolysin Alkeran ; Drug: Mycophenolate mofetil; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: MMF CellCept® ; Drug: Rituxan™; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Rituximab ; Drug: Alemtuzumab; After January 2010, due to the unavailability of muromonab, transplant recipients received a conditioning regimen consisting of systemic chemotherapy and antibodies, including alemtuzumab.; Other Names: Campath-1H Campath® ; Drug: Cyclophosphamide; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Cytoxan ; Drug: Anti-thymocyte globulin (Rabbit); Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Thymoglobulin® Rabbit ATG ; Drug: G-CSF; Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.; Other Names: Filgrastim Neupogen® ; Drug: Muromonab; Prior to January 2010, transplant participants received a conditioning regimen consisting of systemic chemotherapy and antibodies, including muromonab. Muromonab became unavailable from the manufacturer at that time and was replaced by alemtuzumab.; Other Names: OKT3 Muromonab-CD3

Outcome Measures

Primary Outcome Measures

1. Event-free Survival (EFS) [one year post-transplant]

   To determine if one year event-free survival can be improved in pediatric patients undergoing a haploidentical transplant by using a reduced intensity conditioning regimen and a targeted dose T cell depleted donor product. EFS is defined as time from transplantation to the occurrence of relapse or death due to any cause. Patients who are alive at the time of analysis will be censored. The estimated percentage of participants with EFS at one-year post-transplantation is reported using Kaplan-Meier analysis.

Secondary Outcome Measures

1. Overall Survival (OS) [one year post-transplant]

   Estimate the one-year overall survival (OS) for research participants who receive this study treatment. OS is defined as time from transplantation to death due to any cause. Patient who are alive at the time of analysis will be censored. The estimated percentage of participants with OS at one-year post-transplantation is reported using Kaplan-Meier analysis.

2. Disease-Free Survival (DFS) [One year post-transplant]

   Estimate the one-year disease-free survival (DFS) for research participants who receive this study treatment. DFS is defined as time from transplantation to the occurrence of relapse or death due to relapse. Patients who are alive at the time of analysis or die due to other causes will be censored at the time of their events. The estimated percentage of participants with DFS at one-year post-transplantation is reported using Kaplan-Meier analysis.

3. Incidence of Non-hematologic Regimen-related Toxicities [100 days post-transplant]

   Estimate of the incidence of non-hematologic regimen-related toxicity and regimen-related toxicity in the first 100 days post-transplant. The percentage of participants are reported by maximum grade seen using binomial distribution. Participants were graded for toxicity using Common Terminology Criteria for Adverse Events version 3.0. In general, Grade 1 is mild, 2 is moderate toxicity but generally does not require treatment, 3 is severe enough to require treatment, 4 is life-threatening, and 5 means it was associated with death.

4. Incidence of Regimen-related Mortality [100 days post-transplant]

   The incidence of regimen-related mortality in the first 100 days post-transplant is estimated based on binomial distribution.

5. To Estimate the Cumulative Incidence of Relapse for Research Participants Who Receive This Study Treatment. [five years post-transplant]

   The Cumulative Incidence of Relapse will be reported as the proportion of number of relapses since transplant to the total number of patients at risk at five years post-transplant.

6. To Estimate the Rate of Overall Grade III-IV Acute GVHD, and the Rate and Severity of Chronic GVHD in Research Participants. [five years post-transplant]

   The rate of Overall Grade III-IV Acute AVHD will be report as the proportion of patients who have Grade III-IV Acute GVHD to the total patients with transplant. The rate of Chronic GVHD will be report as the proportion of patients who have Chronic GVHD to the total patients with transplant. The Severity of Chronic GVHD will be reported using CTCAE grading system, as a number.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:(transplant recipient)

• Patients less than or equal to 21 years of age; may be greater than 21 years old if a current St. Jude patient or previously treated St. Jude patient within 3 years of completion of prior treatment.

• Must have one of the following diagnosis:

• ALL high risk in second remission. Examples include relapse on therapy, first remission duration of less than or equal to 30 months, or relapse within 12 months of completing therapy.

• ALL in third or subsequent remission.

• ALL high risk in first remission. Examples include: induction failure, minimal residual disease greater than or equal to 1% marrow blasts by morphology after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission.

• High-risk AML in first remission. Examples include monosomy 7, M6, M7, t(6;9), FLT3-ITD, or patients who have greater than or equal to 25% blasts by morphology after induction or who do not achieve CR after 2 courses of therapy (includes myeloid sarcoma).

• Relapsed or persistent AML (less than or equal to 25% blasts in marrow by morphology).

• AML in second or subsequent morphologic remission (includes myeloid sarcoma).

• CML in first chronic phase with detectable molecular or cytogenetic evidence of disease despite medical therapy; or CML with a history of accelerated or blast crisis, now in chronic phase; or unable to tolerate tyrosine kinase inhibitor therapy.

• Juvenile myelomonocytic leukemia (JMML).

• Myelodysplastic syndrome (MDS).

• Therapy related (secondary) AML, ALL, or MDS.

• Hodgkin lymphoma after failure of prior autologous HSCT or unsuitable for autologous HSCT.

• Non-Hodgkin lymphoma (NHL) in second complete remission (CR2) or subsequent.

• Has not received a prior allogeneic hematopoietic stem cell transplant.

• Does not have a suitable HLA-matched sibling donor available for stem cell donation.

• Does not have a suitable cord blood product or volunteer matched unrelated donor (MUD) available in the necessary time for stem cell donation.

• Has a suitable HLA partially matched family member available for stem cell donation.

• Cardiac shortening fraction greater than or equal to 25%.

• Creatinine clearance or glomerular filtration rate (GFR) greater than or equal to 40 ml/min/1.73 m^2.

• Forced vital capacity (FVC) greater than or equal to 40% of predicted value or a pulse oximetry value of greater than or equal to 92% on room air.

• Direct bilirubin less than or equal to 3 mg/dl.

• Age-dependent performance score of greater than or equal to 50.

• Serum glutamic pyruvic transaminase (SGPT) less than 3 times the upper limit of normal for age.

• Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50.

• No known allergy to murine products or human anti-mouse antibody (HAMA) results within normal limits.

• Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment).

• Not breast feeding.

Inclusion criteria (stem cell donor):

• Partially HLA matched family member.

• At least 18 years of age.

• Human immunodeficiency virus (HIV) negative.

• Not pregnant (confirmed by negative serum or urine pregnancy test within 7 days prior to enrollment).

• Not breast feeding.

Inclusion criteria (transplant recipient - stem cell boost)

Has experienced one of the following disorders post-transplant:

• graft failure

• graft rejection

• delayed hematopoietic and/or immune reconstitution.

Exclusion: NA

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Brandon Triplett, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 6, 2016

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00566696
• Other Study ID Numbers: HIFLEX; NCI-2011-03670
• First Posted: Dec 3, 2007
• Last Update Posted: Apr 14, 2020
• Last Verified: Oct 1, 2019

• Keywords provided by St. Jude Children's Research Hospital: Haploidentical stem cell transplant; Allogeneic stem cell transplant; Mismatched family member stem cell donor transplant; Bone marrow transplant; High risk hematologic malignancies; T cell depletion methodology; Miltenyi Biotec CliniMACS stem cell selection device; Campath-1H intravenous
• Additional relevant MeSH terms: Lymphoma; Leukemia; Neoplasms; Preleukemia; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemoglobinuria; Myelodysplastic Syndromes; Hemoglobinuria, Paroxysmal; Mycophenolic Acid; Cyclophosphamide; Melphalan; Mechlorethamine; Thiotepa; Rituximab; Fludarabine; Alemtuzumab; Thymoglobulin; Antilymphocyte Serum; Muromonab-CD3

Study Results

Participant Flow

Recruitment Details	There were 73 enrollments at St. Jude Children's Research Hospital between 12/2007 and 12/2013. Of the 73, 37 were non-patient donors who did not receive therapeutic intervention, and therefore, no outcome data was collected.

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Period Title: Overall Study
STARTED	73
COMPLETED	31
NOT COMPLETED	42

Baseline Characteristics

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Overall Participants	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (4.69)
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	14.2
Sex: Female, Male (Count of Participants)
Female	13 41.9%
Male	18 58.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 35.5%
Not Hispanic or Latino	20 64.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 22.6%
White	20 64.5%
More than one race	1 3.2%
Unknown or Not Reported	2 6.5%
Conditioning Drug Received (participants) [Number]
Muromonab (OKT3)	11 35.5%
Alemtuzumab (Campath-1H)	20 64.5%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival (EFS)
Description	To determine if one year event-free survival can be improved in pediatric patients undergoing a haploidentical transplant by using a reduced intensity conditioning regimen and a targeted dose T cell depleted donor product. EFS is defined as time from transplantation to the occurrence of relapse or death due to any cause. Patients who are alive at the time of analysis will be censored. The estimated percentage of participants with EFS at one-year post-transplantation is reported using Kaplan-Meier analysis.
Time Frame	one year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Number [Percentage of participants]	54.8 176.8%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Estimate the one-year overall survival (OS) for research participants who receive this study treatment. OS is defined as time from transplantation to death due to any cause. Patient who are alive at the time of analysis will be censored. The estimated percentage of participants with OS at one-year post-transplantation is reported using Kaplan-Meier analysis.
Time Frame	one year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Number [Percentage of participants]	71.0 229%

3. Secondary Outcome

Title	Disease-Free Survival (DFS)
Description	Estimate the one-year disease-free survival (DFS) for research participants who receive this study treatment. DFS is defined as time from transplantation to the occurrence of relapse or death due to relapse. Patients who are alive at the time of analysis or die due to other causes will be censored at the time of their events. The estimated percentage of participants with DFS at one-year post-transplantation is reported using Kaplan-Meier analysis.
Time Frame	One year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Number [Percentage of participants]	70.1 226.1%

4. Secondary Outcome

Title	Incidence of Non-hematologic Regimen-related Toxicities
Description	Estimate of the incidence of non-hematologic regimen-related toxicity and regimen-related toxicity in the first 100 days post-transplant. The percentage of participants are reported by maximum grade seen using binomial distribution. Participants were graded for toxicity using Common Terminology Criteria for Adverse Events version 3.0. In general, Grade 1 is mild, 2 is moderate toxicity but generally does not require treatment, 3 is severe enough to require treatment, 4 is life-threatening, and 5 means it was associated with death.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Grade 1	0 0%
Grade 2	3.2 10.3%
Grade 3	61.3 197.7%
Grade 4	19.4 62.6%
Grade 5	16.1 51.9%

5. Secondary Outcome

Title	Incidence of Regimen-related Mortality
Description	The incidence of regimen-related mortality in the first 100 days post-transplant is estimated based on binomial distribution.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Number [Percentage of participants]	9.68 31.2%

6. Secondary Outcome

Title	To Estimate the Cumulative Incidence of Relapse for Research Participants Who Receive This Study Treatment.
Description	The Cumulative Incidence of Relapse will be reported as the proportion of number of relapses since transplant to the total number of patients at risk at five years post-transplant.
Time Frame	five years post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
The Cumulative Incidence of Relapse at five year p	30.0 96.8%
Estimate±SE	8.6 27.7%

7. Secondary Outcome

Title	To Estimate the Rate of Overall Grade III-IV Acute GVHD, and the Rate and Severity of Chronic GVHD in Research Participants.
Description	The rate of Overall Grade III-IV Acute AVHD will be report as the proportion of patients who have Grade III-IV Acute GVHD to the total patients with transplant. The rate of Chronic GVHD will be report as the proportion of patients who have Chronic GVHD to the total patients with transplant. The Severity of Chronic GVHD will be reported using CTCAE grading system, as a number.
Time Frame	five years post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
Measure Participants	31
Rate of Overall Grade III-IV Acute AVHD	22.58 72.8%
Rate of limited grade Chronic GVHD	9.68 31.2%

Adverse Events

Time Frame	Adverse events were collected from the date of participant enrollment through December 23, 2015.
Arm/Group Title	High-Risk Hematologic Malignancies
Arm/Group Description	Participants meeting eligibility criteria and who underwent haploidentical stem cell transplantation with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (beginning January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF.
All Cause Mortality
	High-Risk Hematologic Malignancies
	Affected / at Risk (%)	# Events
Total	16/31 (51.6%)
Serious Adverse Events
	High-Risk Hematologic Malignancies
	Affected / at Risk (%)	# Events
Total	20/31 (64.5%)
Blood and lymphatic system disorders
Graft failure	3/31 (9.7%)	3
Coagulopathy	1/31 (3.2%)	1
Post-transplant lymphoproliferative disease	1/31 (3.2%)	1
Gastrointestinal disorders
Colitis	1/31 (3.2%)	1
Vomiting (disorder)	1/31 (3.2%)	1
General disorders
Fever without neutropenia	9/31 (29%)	11
Headache	1/31 (3.2%)	1
Hepatobiliary disorders
Failure, hepatic	1/31 (3.2%)	1
Veno-occlusive disease, hepatic	2/31 (6.5%)	2
Immune system disorders
Allergic reaction, micafungin	1/31 (3.2%)	1
Infections and infestations
Febrile neutropenia	4/31 (12.9%)	5
Fever without neutropenia	6/31 (19.4%)	6
Hepatitis	1/31 (3.2%)	1
Infection, acinetobacter baumannii, blood	1/31 (3.2%)	1
Infection, aceinetobacter calcoaceticus, baumannii, blood	1/31 (3.2%)	2
Infection, coagulase negative staphylocuccus, skin	1/31 (3.2%)	1
Infection, enterobacter cloacae, blood culture	1/31 (3.2%)	1
Infection, enterococcus faecalis, blood	1/31 (3.2%)	1
Infection, influenza type A, respiratory tract	1/31 (3.2%)	1
Infection, staphylocuccus epidermidis, blood	1/31 (3.2%)	4
Infection, urinary tract, gamma hemolytic streptococcus	1/31 (3.2%)	1
Infection, vancomycin-resistant enterococcus, blood	1/31 (3.2%)	1
Infection, vancomycin resistant enterococcus, blood/Hickman line	1/31 (3.2%)	1
Nervous system disorders
Encephalopathy	2/31 (6.5%)	2
Renal and urinary disorders
Failure, renal	2/31 (6.5%)	2
Hemorrhagic cystitis	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (disorder)	1/31 (3.2%)	1
Skin and subcutaneous tissue disorders
Rash	1/31 (3.2%)	1
Vascular disorders
Hemorrhage, diffuse alveolar	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	High-Risk Hematologic Malignancies
	Affected / at Risk (%)	# Events
Total	30/31 (96.8%)
Blood and lymphatic system disorders
Neutropenia	2/31 (6.5%)	2
Cardiac disorders
Hypertension	6/31 (19.4%)	8
Hypotension	3/31 (9.7%)	3
Gastrointestinal disorders
Mucositis	4/31 (12.9%)	4
Nausea (finding)	3/31 (9.7%)	3
Vomiting (disorder)	2/31 (6.5%)	2
General disorders
Cytokine Release Syndrome (Campath) [10/20 (50%)]	10/20 (50%)	10
Cytokine Release Syndrome (muromonab) [3/11 (27.27%)]	3/11 (27.3%)	3
Cytokine Release Syndrome (Stem Cell Infusion)	3/31 (9.7%)	3
Headache	2/31 (6.5%)	2
Pain, generalized, multiple sites	2/31 (6.5%)	2
Infections and infestations
Febrile neutropenia	24/31 (77.4%)	25
Fever without neutropenia	2/31 (6.5%)	2
Infection, adenovirus, blood	3/31 (9.7%)	3
Infection, adenovirus, respiratory tract	2/31 (6.5%)	2
Infection, adenovirus, stool	4/31 (12.9%)	7
Infection, BK Virus, bladder	2/31 (6.5%)	2
Infection, BK Virus, blood	8/31 (25.8%)	9
Infection, BK Virus, urine	7/31 (22.6%)	8
Infection, Clostridium Difficile, stool	4/31 (12.9%)	5
Infection, herpes simplex, lip	2/31 (6.5%)	2
Infection, Klebsiella pneumoniae, blood	2/31 (6.5%)	2
Infection, vancomycin-resistant enterococcus, rectum	4/31 (12.9%)	4
Metabolism and nutrition disorders
Elevated ALT (SGPT)	3/31 (9.7%)	3
Elevated GGT	3/31 (9.7%)	3
Hyperglycemia	4/31 (12.9%)	4
Hypokalemia (disorder)	5/31 (16.1%)	7
Hypophosphatemia (disorder)	2/31 (6.5%)	2
Nervous system disorders
Confusion	2/31 (6.5%)	2
Encephalopathy	2/31 (6.5%)	2
Renal and urinary disorders
Acute renal failure	2/31 (6.5%)	2
Hemorrhagic cystitis	3/31 (9.7%)	3
Respiratory, thoracic and mediastinal disorders
Hypoxia	4/31 (12.9%)	5
Vascular disorders
Epistaxis	4/31 (12.9%)	4
Hemorrhagic cystitis	2/31 (6.5%)	2

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.