Trial Outcomes & Findings for Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies (NCT NCT01188798)

Last Updated: 2013-03-21

Results Overview

The hypothesis was that individuals receiving the drug pentostatin as GVHD prophylaxis would experience less severe hepatic toxicity than those receiving methotrexate as GVHD prophylaxis. The study is estimated to have sufficient statistical power to ascertain at least a 20% improvement in day 42 grade 2 or above hepatic toxicity-free survival in pentostatin recipients

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

6 participants

Primary outcome timeframe

42 days post-transplant

Results posted on

2013-03-21

Participant Flow

Six transplant patients were recruited between December, 2010 through March, 2011. Participants will be biologically stratified according to disease, donor, and KIR match.

Participant milestones

Participant milestones
Measure	Methotrexate Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Participants were randomized to receive methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Pentostatin Participants will be biologically stratified according to disease, donor, and KIR match between donor and host. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Participants were randomized to receive pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.
Overall Study STARTED	2	4
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Methotrexate Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Participants were randomized to receive methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Pentostatin Participants will be biologically stratified according to disease, donor, and KIR match between donor and host. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Participants were randomized to receive pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.
Overall Study Death	0	1
Overall Study Required additional transplant	1	1
Overall Study Protocol closure	1	1

Baseline Characteristics

Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate n=2 Participants Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Methotrexate: Participants were randomized to receive methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Pentostatin n=4 Participants Participants will be biologically stratified according to disease, donor, and KIR match between donor and host. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Pentostatin: Participants were randomized to receive pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Total n=6 Participants Total of all reporting groups
Age Continuous	10.35 years STANDARD_DEVIATION 0.07 • n=5 Participants	12.95 years STANDARD_DEVIATION 6.65 • n=7 Participants	12.08 years STANDARD_DEVIATION 5.32 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 42 days post-transplant

Population: Insufficient data was available to answer objectives

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days post- transplant

Population: Insufficient data was available to answer objectives.

To characterize the pharmacokinetic-pharmacodynamic relationships of pentostatin in this patient population and to assess the relationship between pre-transplant minimal residual disease (MRD) and transplant outcomes.

Outcome measures

Outcome data not reported

Adverse Events

Methotrexate

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Pentostatin

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate n=2 participants at risk Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Merthotrexate: Participants were randomized to receive methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Pentostatin n=4 participants at risk Participants will be biologically stratified according to disease, donor, and KIR match between donor and host. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Pentostatin: Participants were randomized to receive pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.
Immune system disorders Graft Versus Host Disease (GVHD), Acute, Liver	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Immune system disorders Graft Versus Host Disease (GVHD), Joint, Chronic	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
General disorders Fever without Neutropenia	100.0% 2/2 • Number of events 4 • Adverse events were collected from diagnosis to day 100 post-transplant.	50.0% 2/4 • Number of events 3 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Ulcer of pharynx (disorder)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Hepatobiliary disorders Failure, Hepatic	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Hepatobiliary disorders Veno-occlusive Disease, Hepatic	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Febrile Neutropenia	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Klebsiella, Blood	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Metabolism and nutrition disorders Anemia	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Nervous system disorders Encephalopathy due to vitamin deficiency (disorder)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.

Other adverse events

Additional Information

Asha Pillai, MD

St. Jude Children's Research Hospital

Phone: 1-866-278-5833

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methotrexate n=2 participants at risk Participants will be biologically stratified according to disease, donor, and KIR match. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Merthotrexate: Participants were randomized to receive methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.	Pentostatin n=4 participants at risk Participants will be biologically stratified according to disease, donor, and KIR match between donor and host. In addition to a standard backbone of 2 GVHD prophylactics, a computer generated randomization procedure will assign participants to a third GVHD prophylactic medication (MTX or pentostatin) Pentostatin: Participants were randomized to receive pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.
Immune system disorders Cytokine Release Syndrome (Stem Cell Infusion)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	50.0% 2/4 • Number of events 2 • Adverse events were collected from diagnosis to day 100 post-transplant.
Immune system disorders Cytokine Release Syndrome (Thymoglobulin)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Cardiac disorders Hypertension	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
General disorders Fever without Neutropenia	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Chronic gastritis (disorder)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Gallbladder Disease	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Mucositis	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	50.0% 2/4 • Number of events 2 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Nausea (finding)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Ulcer of pharynx (disorder)	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Gastrointestinal disorders Vomiting (disorder)	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Blood and lymphatic system disorders Bleeding/Hemorrhage, Gastrointestinal	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Blood and lymphatic system disorders Epistaxis	100.0% 2/2 • Number of events 3 • Adverse events were collected from diagnosis to day 100 post-transplant.	50.0% 2/4 • Number of events 2 • Adverse events were collected from diagnosis to day 100 post-transplant.
Blood and lymphatic system disorders Hematemesis	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Blood and lymphatic system disorders Hemorrhagic Cystitis	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Hepatobiliary disorders Typhlitis	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Febrile Neutropenia	100.0% 2/2 • Number of events 5 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Blood and lymphatic system disorders Infection, Adenovirus, Blood	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Adenovirus, Stool	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, BK Virus, Blood	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	50.0% 2/4 • Number of events 2 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, BK Virus, Urine	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Clostridium Difficile, Stool	100.0% 2/2 • Number of events 2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Cytomegalovirus, Urine	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, E. Coli, Blood	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Helicobacter pylori, Stomach	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Herpes Simplex Virus (HSV), Oral	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Pseudomonas Aeruginosa, Blood	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Staphylococcus Epidermidis, Blood	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Infection, Varicella Zoster, Abdomen, Skin	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Infections and infestations Tracheitis	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Metabolism and nutrition disorders Hypertension	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Metabolism and nutrition disorders Metabolic Encephalopathy	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Nervous system disorders Mood Alteration	50.0% 1/2 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.	0.00% 0/4 • Adverse events were collected from diagnosis to day 100 post-transplant.
Nervous system disorders Sensory neuropathy	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Respiratory, thoracic and mediastinal disorders Nodule, Pulmonary, Left Lower Lobe	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Renal and urinary disorders Disease, Renal	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.
Renal and urinary disorders Engraftment Syndrome	0.00% 0/2 • Adverse events were collected from diagnosis to day 100 post-transplant.	25.0% 1/4 • Number of events 1 • Adverse events were collected from diagnosis to day 100 post-transplant.