Trial Outcomes & Findings for Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT (NCT NCT00709592)

NCT ID: NCT00709592

Last Updated: 2018-11-09

Results Overview

A positive test result will indicate immune reconstitution, while a negative test results will indicate lack of immune reconstitution. Participants not done (ND) will be counted with the negative (Neg).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: Up to 9 months following transplant
• Results posted on: 2018-11-09

Participant Flow

Consecutive patients enrolled have recurrent or high-risk hematologic malignancy, adequate end-organ function and performance status. Patient required to have 7/8 or 8/8 mismatched related donor (MRD) or unrelated donor (URD), with high-resolution typing performed for HLA-A, -B, -C, and -DRB1.

Randomized to rabbit ATG (Thymoglobulin; Genzyme, Cambridge, MA), 2.5 or 1.7 mg/kg adjusted ideal body weight/day, followed by TBI to a total dose of 4.5 Gy. Methylprednisolone 2 mg/kg given pre-medication for ATG. GVHD prophylaxis was tacrolimus starting at approximately 12 weeks post transplantation.

Participant milestones

Measure	A:Thymoglobulin: 1.7 mg/kg/Day 1.7 mg/kg/d thymoglobulin IV d-9 to -7	B:Thymoglobulin: 2.5 mg/kg/Day 2.5 mg/kg/d thymoglobulin IV d-9 to d-7
Overall Study STARTED	19	23
Overall Study COMPLETED	19	22
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	A:Thymoglobulin: 1.7 mg/kg/Day 1.7 mg/kg/d thymoglobulin IV d-9 to -7	B:Thymoglobulin: 2.5 mg/kg/Day 2.5 mg/kg/d thymoglobulin IV d-9 to d-7
Overall Study Unable to proceed to transplant	0	1

Baseline Characteristics

Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

Baseline characteristics by cohort

Measure	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7	B:Thymoglobulin: 2.5 mg/kg/Day n=23 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	Total n=42 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	57 years n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	23 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 9 months following transplant

A positive test result will indicate immune reconstitution, while a negative test results will indicate lack of immune reconstitution. Participants not done (ND) will be counted with the negative (Neg).

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine. Positive	3 participants	8 participants
The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine. Negative/Not Done	19 participants	11 participants

SECONDARY outcome

Timeframe: Up to 52 weeks post transplant.

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.	12 Days Interval 10.0 to 37.0	12 Days Interval 10.0 to 37.0

SECONDARY outcome

Timeframe: 2-year survival rate (%)

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Survival	62.4 percentage of patient surviving	71.3 percentage of patient surviving

SECONDARY outcome

Timeframe: Day 100

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Treatment Related Mortality	0 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Event-free Survival	44.5 percentage of participants	62.2 percentage of participants

SECONDARY outcome

Timeframe: 2 year relapse rate (%)

Patients with different disease relapses was determined according to current clinical standards based on the disease. For example, AML or MDS relapse is determined by a bone marrow biopsy. Multiple myeloma relapse requires a number of labs and/or biopsy to diagnose such as SPEP, UPEP, immunofixation, serum and urine light chains. In lymphoma disease is followed using CT and/or PET scans.

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Relapse	50 Percent patients relapsing	28 Percent patients relapsing

SECONDARY outcome

Timeframe: 2 year rate of DLI

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Donor Lymphocyte Infusion	45.5 percentage of participants	8.9 percentage of participants

SECONDARY outcome

Timeframe: 2 year rate (%)

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Acute Graft-Versus-Host Disease (GVHD)	4.5 percentage of participant	27.2 percentage of participant

SECONDARY outcome

Timeframe: 2 year GVHD rate

Outcome measures

Measure	B:Thymoglobulin: 2.5 mg/kg/Day n=22 Participants 2.5 mg/kg/d thymoglobulin IV d-9 to d-7	A:Thymoglobulin: 1.7 mg/kg/Day n=19 Participants 1.7 mg/kg/d thymoglobulin IV d-9 to -7
Chronic Graft-Versus-Host Disease (GVHD)	31.8 percentage of participants	23.8 percentage of participants

Adverse Events

A:Thymoglobulin: 1.7 mg/kg/Day

Serious events: 7 serious events

Other events: 19 other events

Deaths: 0 deaths

B:Thymoglobulin: 2.5 mg/kg/Day

Serious events: 12 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	A:Thymoglobulin: 1.7 mg/kg/Day n=19 participants at risk 1.7 mg/kg/d thymoglobulin IV d-9 to -7	B:Thymoglobulin: 2.5 mg/kg/Day n=22 participants at risk 2.5 mg/kg/d thymoglobulin IV d-9 to d-7
Nervous system disorders Syncope	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Hepatic	10.5% 2/19 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Nervous system disorders CNS toxicity	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Cardiac disorders Cardiac dysrhythmia	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Diarrhea	15.8% 3/19 • Number of events 3 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Renal and urinary disorders Hemorrhagic cystitis	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Infections and infestations Fever with out bacteremia	10.5% 2/19 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	9.1% 2/22 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Infections and infestations Fever with Bacteremia +/- abscess	15.8% 3/19 • Number of events 3 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	27.3% 6/22 • Number of events 6 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Intra-abdominal	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Nervous system disorders Brain abscess	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Nausea	0.00% 0/19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	9.1% 2/22 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Renal and urinary disorders Renal	10.5% 2/19 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Renal and urinary disorders Hyponatremia	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.

Other adverse events

Measure	A:Thymoglobulin: 1.7 mg/kg/Day n=19 participants at risk 1.7 mg/kg/d thymoglobulin IV d-9 to -7	B:Thymoglobulin: 2.5 mg/kg/Day n=22 participants at risk 2.5 mg/kg/d thymoglobulin IV d-9 to d-7
Blood and lymphatic system disorders Grade 3 neutropenia	100.0% 19/19 • Number of events 19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	100.0% 22/22 • Number of events 22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Blood and lymphatic system disorders Lymphopenia post conditioning	100.0% 19/19 • Number of events 19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	100.0% 22/22 • Number of events 22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 19/19 • Number of events 19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	100.0% 22/22 • Number of events 22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Eye disorders Ocular	0.00% 0/19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	9.1% 2/22 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Blood and lymphatic system disorders Post transplant neutropenia	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Infections and infestations Bacteremia/Fever	10.5% 2/19 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Skin and subcutaneous tissue disorders Rash	0.00% 0/19 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 2 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Gastrointestinal disorders Diarrhea	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	4.5% 1/22 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.
Renal and urinary disorders Urinary tract infection	5.3% 1/19 • Number of events 1 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.	0.00% 0/22 • All events collected from first patient accrual up to day 180 or relapse for each subject on each arm. Still collecting SAEs, subjects on trial until death.

Additional Information

Amir A Toor, MD

Virginia Commonwealth University

Phone: 804-828-4360

Email: atoor@mcvh-vcu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place