Trial Outcomes & Findings for Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies (NCT NCT00566696)

Last Updated: 2020-04-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

one year post-transplant

Results posted on

2020-04-14

Participant Flow

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.

Participant milestones

Participant milestones
Measure	High-Risk Hematologic Malignancies 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 Study STARTED	73
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	42

Reasons for withdrawal

Reasons for withdrawal
Measure	High-Risk Hematologic Malignancies 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 Study Met Exclusion Criteria	2
Overall Study Muromonab not available	1
Overall Study Health Status Change	1
Overall Study Physician Decision	1
Overall Study Non-Patient Donors	37

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
Age, Continuous	13.3 years STANDARD_DEVIATION 4.69 • n=5 Participants
Age, Customized	14.2 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Conditioning Drug Received Muromonab (OKT3)	11 participants n=5 Participants
Conditioning Drug Received Alemtuzumab (Campath-1H)	20 participants n=5 Participants

PRIMARY outcome

Timeframe: one year post-transplant

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
Event-free Survival (EFS)	54.8 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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 Survival (OS)	71.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
Disease-Free Survival (DFS)	70.1 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
Incidence of Non-hematologic Regimen-related Toxicities Grade 1	0 percentage of participants
Incidence of Non-hematologic Regimen-related Toxicities Grade 2	3.2 percentage of participants
Incidence of Non-hematologic Regimen-related Toxicities Grade 3	61.3 percentage of participants
Incidence of Non-hematologic Regimen-related Toxicities Grade 4	19.4 percentage of participants
Incidence of Non-hematologic Regimen-related Toxicities Grade 5	16.1 percentage of participants

SECONDARY outcome

Timeframe: 100 days post-transplant

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

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
Incidence of Regimen-related Mortality	9.68 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
To Estimate the Cumulative Incidence of Relapse for Research Participants Who Receive This Study Treatment. The Cumulative Incidence of Relapse at five year p	30.0 Percentage of participants
To Estimate the Cumulative Incidence of Relapse for Research Participants Who Receive This Study Treatment. Estimate±SE	8.6 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-Risk Hematologic Malignancies n=31 Participants 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.
To Estimate the Rate of Overall Grade III-IV Acute GVHD, and the Rate and Severity of Chronic GVHD in Research Participants. Rate of Overall Grade III-IV Acute AVHD	22.58 Percentage of participants
To Estimate the Rate of Overall Grade III-IV Acute GVHD, and the Rate and Severity of Chronic GVHD in Research Participants. Rate of limited grade Chronic GVHD	9.68 Percentage of participants

Adverse Events

High-Risk Hematologic Malignancies

Serious events: 20 serious events

Other events: 30 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	High-Risk Hematologic Malignancies n=31 participants at risk 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.
Immune system disorders Allergic reaction, micafungin	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Blood and lymphatic system disorders Graft failure	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Blood and lymphatic system disorders Coagulopathy	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Blood and lymphatic system disorders Post-transplant lymphoproliferative disease	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Fever without neutropenia	29.0% 9/31 • Number of events 11 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Headache	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Skin and subcutaneous tissue disorders Rash	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Gastrointestinal disorders Colitis	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Gastrointestinal disorders Vomiting (disorder)	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Vascular disorders Hemorrhage, diffuse alveolar	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Hepatobiliary disorders Failure, hepatic	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Hepatobiliary disorders Veno-occlusive disease, hepatic	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Nervous system disorders Encephalopathy	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome (disorder)	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Renal and urinary disorders Failure, renal	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Renal and urinary disorders Hemorrhagic cystitis	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Febrile neutropenia	12.9% 4/31 • Number of events 5 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Fever without neutropenia	19.4% 6/31 • Number of events 6 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Hepatitis	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, acinetobacter baumannii, blood	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, aceinetobacter calcoaceticus, baumannii, blood	3.2% 1/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, coagulase negative staphylocuccus, skin	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, enterobacter cloacae, blood culture	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, enterococcus faecalis, blood	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, influenza type A, respiratory tract	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, staphylocuccus epidermidis, blood	3.2% 1/31 • Number of events 4 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, urinary tract, gamma hemolytic streptococcus	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, vancomycin-resistant enterococcus, blood	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, vancomycin resistant enterococcus, blood/Hickman line	3.2% 1/31 • Number of events 1 • Adverse events were collected from the date of participant enrollment through December 23, 2015.

Other adverse events

Other adverse events
Measure	High-Risk Hematologic Malignancies n=31 participants at risk 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.
Blood and lymphatic system disorders Neutropenia	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Cardiac disorders Hypertension	19.4% 6/31 • Number of events 8 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Cardiac disorders Hypotension	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Gastrointestinal disorders Mucositis	12.9% 4/31 • Number of events 4 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Gastrointestinal disorders Nausea (finding)	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Gastrointestinal disorders Vomiting (disorder)	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Vascular disorders Epistaxis	12.9% 4/31 • Number of events 4 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Vascular disorders Hemorrhagic cystitis	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Metabolism and nutrition disorders Elevated ALT (SGPT)	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Metabolism and nutrition disorders Elevated GGT	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Metabolism and nutrition disorders Hyperglycemia	12.9% 4/31 • Number of events 4 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Metabolism and nutrition disorders Hypokalemia (disorder)	16.1% 5/31 • Number of events 7 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Metabolism and nutrition disorders Hypophosphatemia (disorder)	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Nervous system disorders Confusion	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Nervous system disorders Encephalopathy	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Respiratory, thoracic and mediastinal disorders Hypoxia	12.9% 4/31 • Number of events 5 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Renal and urinary disorders Acute renal failure	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Renal and urinary disorders Hemorrhagic cystitis	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Cytokine Release Syndrome (Campath) [10/20 (50%)]	50.0% 10/20 • Number of events 10 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Cytokine Release Syndrome (muromonab) [3/11 (27.27%)]	27.3% 3/11 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Cytokine Release Syndrome (Stem Cell Infusion)	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Headache	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
General disorders Pain, generalized, multiple sites	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Febrile neutropenia	77.4% 24/31 • Number of events 25 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Fever without neutropenia	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, adenovirus, blood	9.7% 3/31 • Number of events 3 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, adenovirus, respiratory tract	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, adenovirus, stool	12.9% 4/31 • Number of events 7 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, BK Virus, bladder	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, BK Virus, blood	25.8% 8/31 • Number of events 9 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, BK Virus, urine	22.6% 7/31 • Number of events 8 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, Clostridium Difficile, stool	12.9% 4/31 • Number of events 5 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, herpes simplex, lip	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, Klebsiella pneumoniae, blood	6.5% 2/31 • Number of events 2 • Adverse events were collected from the date of participant enrollment through December 23, 2015.
Infections and infestations Infection, vancomycin-resistant enterococcus, rectum	12.9% 4/31 • Number of events 4 • Adverse events were collected from the date of participant enrollment through December 23, 2015.

Additional Information

Brandon Triplett, MD

St. Jude Children's Research Hospital

Phone: 866-278-5833

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place