Acute Lymphoblastic LeukemiaPhase 3NCT01188798
Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
A Phase 3 study testing Methotrexate and Pentostatin in people with Acute Lymphoblastic Leukemia and Acute Myelocytic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 months to 21 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myelocytic Leukemia, Chronic Myelocytic Leukemia
- What is being tested?
- Methotrexate and Pentostatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Feb 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 26Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
St . Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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
- Acute Lymphoblastic Leukemia, Acute Myelocytic Leukemia, Chronic Myelocytic Leukemia, Hodgkin's Disease, Myelodysplastic Syndrome
- Being tested
- Methotrexate, Pentostatin
- Keywords
- Allogeneic Bone Marrow Transplantation, Graft versus host disease, Tacrolimus, Sirolimus, Methotrexate, Pentostatin
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hodgkin Disease, Myelodysplastic Syndromes, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
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.
PentostatinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Transplant recipients receiving Methotrexate | Experimental | 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) Receives: Drug: Methotrexate |
| Transplant recipients receiving Pentostatin | Experimental | 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) Receives: Drug: Pentostatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 42 days post-transplant
Secondary outcomes (1)
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.
Measured: 42 days post- transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Asha Pillai, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01188798
- Sponsor's protocol ID
- MUDSIB
- Status last verified
- Feb 2012
- First submitted
- 24 Aug 2010
- Last updated
- 21 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01188798
- Acronym / sponsor ID
- MUDSIB
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myelocytic Leukemia, Chronic Myelocytic Leukemia, Hodgkin's Disease, Myelodysplastic Syndrome
- Keywords
- Allogeneic Bone Marrow Transplantation, Graft versus host disease, Tacrolimus, Sirolimus, Methotrexate, Pentostatin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 25 Aug 2010 (estimated)
- Results
- Posted 14 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transplant recipients receiving Methotrexate | Experimental | Drug: MethotrexateParticipants 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) |
| Transplant recipients receiving Pentostatin | Experimental | Drug: PentostatinParticipants 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) |
Who may qualify
- Ages
- 18 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (26 listed)
- Age less than or equal to 21 years old
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateParticipants 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. | Drug | Transplant recipients receiving Methotrexate |
| PentostatinParticipants 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. | Drug | Transplant recipients receiving Pentostatin |
Primary outcome
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.
Time frame: 42 days post-transplant
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
1 secondary outcome
Assess Overall Survival, Relapse, Engraftment, and Regimen-related Morbidity and Estimating Cumulative Incidence of Pulmonary Adverse Events and Mucositis.
Time frame: 42 days post- transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asha Pillai, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate and Pentostatin in people with Acute Lymphoblastic Leukemia and Acute Myelocytic Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 42 days post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2013; AzTrials last refreshed its copy on 26 Oct 2026.