CompletedNCT01188798Updated Mar 21, 2013Results posted

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

A Phase 3 interventional study of Methotrexate and Pentostatin in Acute Lymphoblastic Leukemia, Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia, sponsored by St. Jude Children's Research Hospital. Completed at 1 site in United States. Open to participants aged 18 Months to 21 Years. Per ClinicalTrials.gov, last updated 2013-03-21.

Sponsored by St. Jude Children's Research Hospital · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 6
Allocation: Randomized
Ages: 18 Months to 21 Years
Sex: All

Study summary

The purpose of the study is to determine if participants who receive the GVHD prophylaxis medication pentostatin will have less severe hepatic toxicities than those receiving MTX. The study is estimated to have sufficient statistical power to ascertain at least a 20% improvement in day 42 NCI CTC grade 2 or above hepatic toxicity-free survival in pentostatin recipients.

Read the detailed description

Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor. All participants will receive a standard backbone GVHD prophylaxis regimen (tacrolimus and sirolimus) and conditioning (cyclophosphamide/TBI). A risk-adapted approach will be used during conditioning to further minimize the risk of leukemia relapse based on two factors:

Lymphoid versus myeloid primary disease.
KIR compatibility between donor and host.

Conditions studied

Acute Lymphoblastic Leukemia
Acute Myelocytic Leukemia
Chronic Myelocytic Leukemia
Hodgkin's Disease
Myelodysplastic Syndrome

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Keywords

Allogeneic Bone Marrow Transplantation
Graft versus host disease
Tacrolimus
Sirolimus
Methotrexate
Pentostatin

In context

Precursor Cell Lymphoblastic Leukemia-Lymphoma

2,121 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 492 are open to participants now.

This study's enrollment of 6 is below the median of 40 across 1,691 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.

Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →

Lead sponsor

St. Jude Children's Research Hospital is the lead sponsor of 439 studies on the registry; 101 are open to participants now.

Of its 61 completed or terminated interventional studies of FDA-regulated products, 37 (61%) have results posted.

Browse St. Jude Children's Research Hospital studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Months to 21 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

*Age less than or equal to 21 years old

High risk malignancy as follows:

High-risk ALL in CR1. Examples include, but not limited to: Induction failure or > 1% leukemic lymphoblasts in the bone marrow on remission date;> 0.1% leukemic lymphoblasts in the bone marrow in week 7 of continuation treatment (i.e. before reinduction I); re-emergence of leukemic lymphoblasts by MRD (at any level) in patients previously MRD negative; persistently detectable MRD at lower levels;early T-cell precursor (ETP) ALL.
High-risk ALL beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
High-risk de novo AML in CR1.Examples include but are not limited to:evidence of a high-risk genetic abnormality or high-risk MRD features.
AML beyond CR1, or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state. "Refractory disease" includes induction failure.
Therapy-related AML.
MDS, primary or secondary, at any stage.
NK cell lymphoblastic leukemia in any CR
Biphenotypic bilineage, or undifferentiated leukemia.
CML in any phase
Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
Non-Hodgkin lymphoma beyond CR1 or with refractory disease. "Beyond CR1" denotes any CR following CR1, or any relapsed state.
Juvenile Myelomonocytic Leukemia (JMML).
All patients with prior evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
Has a suitable HLA matched sibling or unrelated volunteer donor available for stem cell donation.A "matched" donor is defined as allele matching at 7/8 to 8/8 HLA loci at A, B, C and DRB1.For the purpose of this study, the term "matched sibling" also refers to an HLA matched family member.
Does not have any other active malignancy other than the one for which this transplant is indicated.
Left ventricular ejection fraction > 40%,or shortening fraction > 26%.
Forced vital capacity (FVC) greater than or equal to 50% of predicted value (corrected for hemoglobin), or if patient is unable to perform pulmonary function testing, pulse oximetry greater than or equal to 92% on room air.
Creatinine clearance greater than or equal to 70 ml/min/1.73m2
Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 70.
Bilirubin less than or equal to 2.5 mg/dL.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than or equal to 5 times upper limit of normal
Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
Not lactating.
Has not had a prior allogeneic HSCT.

Exclusion criteria

Exclusion Criteria:

Pregnant and lactating females are excluded from participation as the short and long-term effects of the protocol interventions and infusion on a fetus or a nursing child through breast milk are not entirely known at this time.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 6 participants (actual)

Study arms

Experimental
Transplant recipients receiving 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)
Drug: Methotrexate
Experimental
Transplant recipients receiving 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)
Drug: Pentostatin

Interventions

DrugMethotrexate
Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.
DrugPentostatin
Participants will be randomized to receive either methotrexate (MTX) or pentostatin for graft-versus-host disease (GVHD) prophylaxis after receiving an allogeneic bone marrow transplant from an HLA-matched related or unrelated donor.

What researchers measure

Primary outcomes

Determining Whether the Hepatic Adverse Event-free (NCI Grades II-IV) Survival at Day 42 After an HLA-matched Transplant for Hematologic Malignancy Can be Improved by Using a GVHD Prophylaxis Regimen That Includes Pentostatin Rather Than MTX.
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
Time frame: 42 days post-transplant

Secondary outcomes

Assess Overall Survival, Relapse, Engraftment, and Regimen-related Morbidity and Estimating Cumulative Incidence of Pulmonary Adverse Events and Mucositis.
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.
Time frame: 42 days post- transplant

Results

Posted Mar 14, 2013

Limitations and caveats

This study was terminated prematurely. The Data Safety and Monitoring Board (DSMB) requested major scientific study changes. This was deemed infeasible by institutional leadership and study was terminated. Therefore, no final results exist to report.

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 flow — Overall Study
Milestone	Methotrexate	Pentostatin
Started	2	4
Completed	0	1
Not completed	2	3
Withdrew: Death	0	1
Withdrew: Required additional transplant	1	1
Withdrew: Protocol closure	1	1

Outcome measures

PrimaryDetermining Whether the Hepatic Adverse Event-free (NCI Grades II-IV) Survival at Day 42 After an HLA-matched Transplant for Hematologic Malignancy Can be Improved by Using a GVHD Prophylaxis Regimen That Includes Pentostatin Rather Than MTX.

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

Time frame:: 42 days post-transplant

No measurements were reported for this outcome.

SecondaryAssess Overall Survival, Relapse, Engraftment, and Regimen-related Morbidity and Estimating Cumulative Incidence of Pulmonary Adverse Events and Mucositis.

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.

Time frame:: 42 days post- transplant

No measurements were reported for this outcome.

Adverse events

Collected over Adverse events were collected from diagnosis to day 100 post-transplant.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Methotrexate	—	2/2 (100%)	2/2 (100%)
Pentostatin	—	4/4 (100%)	4/4 (100%)

Most frequent serious events

Most frequent serious events
Event	Methotrexate	Pentostatin
Fever without NeutropeniaGeneral disorders	2/2	2/4
Graft Versus Host Disease (GVHD), Acute, LiverImmune system disorders	0/2	1/4
Graft Versus Host Disease (GVHD), Joint, ChronicImmune system disorders	0/2	1/4
Ulcer of pharynx (disorder)Gastrointestinal disorders	0/2	1/4
Failure, HepaticHepatobiliary disorders	0/2	1/4
Veno-occlusive Disease, HepaticHepatobiliary disorders	0/2	1/4
Febrile NeutropeniaInfections and infestations	0/2	1/4
Infection, Klebsiella, BloodInfections and infestations	0/2	1/4
AnemiaMetabolism and nutrition disorders	0/2	1/4
Encephalopathy due to vitamin deficiency (disorder)Nervous system disorders	0/2	1/4

Most frequent other events

Showing 10 of 38

Most frequent other events
Event	Methotrexate	Pentostatin
EpistaxisBlood and lymphatic system disorders	2/2	2/4
Febrile NeutropeniaInfections and infestations	2/2	1/4
Infection, Clostridium Difficile, StoolInfections and infestations	2/2	1/4
Cytokine Release Syndrome (Stem Cell Infusion)Immune system disorders	0/2	2/4
HypertensionCardiac disorders	1/2	1/4
Fever without NeutropeniaGeneral disorders	1/2	0/4
MucositisGastrointestinal disorders	1/2	2/4
Ulcer of pharynx (disorder)Gastrointestinal disorders	1/2	0/4
HematemesisBlood and lymphatic system disorders	1/2	0/4
Infection, Adenovirus, StoolInfections and infestations	1/2	1/4

Baseline characteristics

Age Continuous
Age Continuous(years)	Methotrexate	Pentostatin	Total
Mean	10.35 ± 0.07	12.95 ± 6.65	12.08 ± 5.32

Sex: Female, Male
Sex: Female, Male(Participants)	Methotrexate	Pentostatin	Total
Female	1	4	5
Male	1	0	1

Study locations

1 site

St . Jude Children's Research Hospital
Memphis, Tennessee 38105, United States

References and documents

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Sep 2010, a primary completion of Feb 2012 and a completion of Feb 2012. It does not say whether these dates are actual or estimated.

Results were first posted in Mar 2013, 1 year 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Aug 24, 2010
First posted: Aug 25, 2010
Start: Sep 2010
Primary completionActual: Feb 2012
CompletionActual: Feb 2012
Results first posted: Mar 14, 2013
Last update: Mar 21, 2013

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Mar 21, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01188798
Lead sponsor: St. Jude Children's Research Hospital
Responsible party: Sponsor
First posted: Aug 25, 2010
Start date: Sep 2010
Primary completion: Feb 2012
Completion: Feb 2012
Results posted: Mar 14, 2013
Last update: Mar 21, 2013

Study contacts

Asha Pillai, MD

principal investigator · St. Jude Children's Research Hospital

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2012. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Methotrexate · Pentostatin

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