NCT00709592

Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

Completed Phase 2 Results posted Last updated 9 November 2018

What this trial tests

Phase 2 trial testing Thymoglobulin in Non-Hodgkin's Lymphoma in 42 participants. Completed in 28 June 2017.

Timeline

21 July 2008

Primary endpoint
15 February 2014

28 June 2017

Quick facts

Lead sponsor	Virginia Commonwealth University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	42
Start date	21 July 2008
Primary completion	15 February 2014
Estimated completion	28 June 2017
Sites	1 location across United States

Drugs / interventions tested

• Thymoglobulin — full drug profile →
• Total-Body Irradiation
• Allogeneic PBSCT or BMT
• Tacrolimus (TACROLIMUS) — full drug profile →
• Mycophenolate Mofetil (MYCOPHENOLATE MOFETIL) — full drug profile →

Conditions studied

• Non-Hodgkin's Lymphoma — all drugs for Non-Hodgkin's Lymphoma →
• Leukemia — all drugs for Leukemia →
• Multiple Myeloma — all drugs for Multiple Myeloma →
• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →

Sponsor

Virginia Commonwealth University

Who can join

Adults 40 to 70, any sex, with Non-Hodgkin's Lymphoma or Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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. Primary · 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).

Positive

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	8
B:Thymoglobulin: 2.5 mg/kg/Day	3

Negative/Not Done

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	11
B:Thymoglobulin: 2.5 mg/kg/Day	19

Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT. Secondary · Up to 52 weeks post transplant.

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	12	10 – 37
B:Thymoglobulin: 2.5 mg/kg/Day	12	10 – 37

Survival Secondary · 2-year survival rate (%)

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	71.3
B:Thymoglobulin: 2.5 mg/kg/Day	62.4

Treatment Related Mortality Secondary · Day 100

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	0
B:Thymoglobulin: 2.5 mg/kg/Day	0

Event-free Survival Secondary · 2 years

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	62.2
B:Thymoglobulin: 2.5 mg/kg/Day	44.5

Relapse Secondary · 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.

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	28
B:Thymoglobulin: 2.5 mg/kg/Day	50

Donor Lymphocyte Infusion Secondary · 2 year rate of DLI

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	8.9
B:Thymoglobulin: 2.5 mg/kg/Day	45.5

Acute Graft-Versus-Host Disease (GVHD) Secondary · 2 year rate (%)

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	27.2
B:Thymoglobulin: 2.5 mg/kg/Day	4.5

Chronic Graft-Versus-Host Disease (GVHD) Secondary · 2 year GVHD rate

Group	Value	95% CI
A:Thymoglobulin: 1.7 mg/kg/Day	23.8
B:Thymoglobulin: 2.5 mg/kg/Day	31.8

Adverse events — posted to ClinicalTrials.gov

Time frame: All events collected from first patient accrual up to day 180 or relapse for each subject on each arm.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

A:Thymoglobulin: 1.7 mg/kg/Day

Serious: 7/19 (37%)

Deaths: —

B:Thymoglobulin: 2.5 mg/kg/Day

Serious: 12/22 (55%)

Deaths: —

Serious adverse events (13 terms)

Reaction	System	A:Thymoglobulin: 1.7 mg/kg…	B:Thymoglobulin: 2.5 mg/kg…
Fever with Bacteremia +/- abscess	Infections and infestations	—	—
Diarrhea	Gastrointestinal disorders	—	—
Hepatic	Gastrointestinal disorders	—	—
Fever with out bacteremia	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Renal	Renal and urinary disorders	—	—
Syncope	Nervous system disorders	—	—
CNS toxicity	Nervous system disorders	—	—
Cardiac dysrhythmia	Cardiac disorders	—	—
Hemorrhagic cystitis	Renal and urinary disorders	—	—
Intra-abdominal	Gastrointestinal disorders	—	—
Brain abscess	Nervous system disorders	—	—
Hyponatremia	Renal and urinary disorders	—	—

Other adverse events (10 terms — click to expand)

Reaction	System	A:Thymoglobulin: 1.7 mg/kg…	B:Thymoglobulin: 2.5 mg/kg…
Grade 3 neutropenia	Blood and lymphatic system disorders	—	—
Lymphopenia post conditioning	Blood and lymphatic system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Ocular	Eye disorders	—	—
Bacteremia/Fever	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Post transplant neutropenia	Blood and lymphatic system disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Urinary tract infection	Renal and urinary disorders	—	—

Most-reported serious reactions: Fever with Bacteremia +/- abscess, Diarrhea, Hepatic, Fever with out bacteremia, Nausea, Renal, Syncope, CNS toxicity.

Data from ClinicalTrials.gov NCT00709592 adverse events section.

Sponsor's own description

One of two different doses of thymoglobulin will allow bone marrow engraftment with minimal Graft-versus-Host Disease and allow adequate immune response to allow the transplanted stem cells to replace the tumor cells.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.
   Toor AA, Sabo RT, Roberts CH, Moore BL, et al · · 2015 · cited 27× · PMID 25849208 · DOI 10.1016/j.bbmt.2015.03.011
2. In silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem-Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation.
   Jameson-Lee M, Koparde V, Griffith P, Scalora AF, et al · · 2014 · cited 20× · PMID 25414699 · DOI 10.3389/fimmu.2014.00529
3. Favorable outcomes in patients with high donor-derived T cell count after in vivo T cell-depleted reduced-intensity allogeneic stem cell transplantation.
   Toor AA, Sabo RT, Chung HM, Roberts C, et al · · 2012 · cited 13× · PMID 22005648 · DOI 10.1016/j.bbmt.2011.10.011
4. Stem cell transplantation as a dynamical system: are clinical outcomes deterministic?
   Toor AA, Kobulnicky JD, Salman S, Roberts CH, et al · · 2014 · cited 11× · PMID 25520720 · DOI 10.3389/fimmu.2014.00613
5. On the organization of human T-cell receptor loci: log-periodic distribution of T-cell receptor gene segments.
   Toor AA, Toor AA, Rahmani M, Manjili MH. · · 2016 · cited 4× · PMID 26763333 · DOI 10.1098/rsif.2015.0911