LeukemiaPhase 1/2NCT00506922
Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT
A Phase 1/2 study testing Pentostatin, Tacrolimus and Methotrexate in people with Leukemia and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objective: 1. To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation. Secondary Objectives: 1. Read more about this study
- Who is it for?
- Any age
- What is being tested?
- Pentostatin, Tacrolimus and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2000to Nov 2009
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.
- Patients with AML, ALL, Hodgkin's disease, MDS (including CMML), CML in late chronic or accelerated phase or in blast crisis, and lymphoma in first or later relapses.
- Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.
- Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.
Who cannot join
- HIV seropositivity
- Uncontrolled infection
- Pregnancy
- Candidates should not have received chemotherapy other than hydroxyurea or Gleevec for at least 3 weeks prior to treatment. Maintenance therapy with oral chemotherapy is acceptable. Treatment day is defined as transplant day +8, which is the date of first dose of pentostatin.
- Diagnosis of myelofibrosis.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation
Primary Objective:
- To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation.
Secondary Objectives:
- To determine safety of escalating doses of pentostatin in combination with tacrolimus and methotrexate.
- To reduce the incidence of acute GVHD following transplants with unrelated donor to 40%.
- To document blood levels of tacrolimus when combined with pentostatin.
Read the detailed description
During the study, patients will have blood, urine, bone marrow, and X-ray exams done. These exams are done to monitor the results of the transplantation. Blood tests will be done daily while patients are hospitalized.
Patients in this study will receive chemotherapy and/or radiation to treat their malignancy and prevent graft rejection. This is given before the infusion of donor cells.
Patients with myeloid leukemias may receive busulfan by vein (IV) for 4 days and cyclophosphamide by vein for 2 days.
Patients with lymphoid malignancies may receive thiotepa by vein in one dose, cyclophosphamide by vein for 2 days, and irradiation for 4 days.
Other chemotherapy treatments may be used before donor cell infusion.
IV injections will be given through a previously inserted catheter that extends into the vena cava (a large chest vein).
Patients will be randomly picked (as in the toss of a coin) to receive one of five different treatments. This is done to learn the benefit of pentostatin treatment and the appropriate dose. Four of the treatments will use different dose schedules of pentostatin. The fifth treatment group will receive no pentostatin at all. All patients receive tacrolimus and methotrexate.
Pentostatin will be given by vein in 4 doses during the first month after transplant. Tacrolimus (FK506) will be given by vein or mouth for 6 months. Methotrexate will be given by vein for 3 doses in the first week after transplant.
Patients will receive blood and platelet transfusions after the transplant. The number of transfusions will depend on how quickly the blood cell counts return to a normal range.
Patients will remain in the hospital for about 4-6 weeks and in the Houston area for 100 days after the transplant.
This is an investigational study. All of the study drugs are commercially available. Pentostatin will not be used for GVHD prevention outside of this study. A total of 150 patients will take part in this study.
- Being tested
- Pentostatin, Tacrolimus, Methotrexate
- Keywords
- Graft-Versus-Host Disease, GVHD Prevention, Hodgkin's Disease, Leukemia, Lymphoma, Methotrexate, Tacrolimus, Pentostatin
- Medical subject headings
- Leukemia, Lymphoma, Graft vs Host Disease, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentostatinDrug
Also called Nipent, Deoxycoformycin, DCF
Given intravenously on days +8, +15, +22 and +30 post transplant:
Group 2 - Pentostatin 0.5 mg/m^2
Group 3 - Pentostatin 1 mg/m^2
Group 4 - Pentostatin 1.5 mg/m^2
Group 5 - Pentostatin 2 mg/m^2
TacrolimusDrug
Also called Prograf
Given intravenously from day -2, and will be switched to oral dosing when tolerated.
MethotrexateDrug
Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| No Pentostatin | Experimental | Group 1: No Pentostatin Receives: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate |
| Pentostatin 0.5 | Experimental | Group 2: Pentostatin 0.5 mg/m^2 Receives: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate |
| Pentostatin 1 | Experimental | Group 3: Pentostatin 1 mg/m^2 Receives: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate |
| Pentostatin 1.5 | Experimental | Group 4: Pentostatin 1.5 mg/m^2 Receives: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate |
| Pentostatin 2 | Experimental | Group 5: Pentostatin 2 mg/m^2 Receives: Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Without GVHD at 100 Days
The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2007 (estimated)
- Study startSep 2000
- Primary completionNov 2009
- Study completionNov 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Marcos de Lima, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00506922
- Sponsor's protocol ID
- ID00-132
- Status last verified
- Aug 2012
- First submitted
- 20 Jul 2007
- Last updated
- 28 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Parmar S, Del Lima M, Zou Y, Patah PA, Liu P, Cano P, Rondon G, Pesoa S, de Padua Silva L, Qazilbash MH, Hosing C, Popat U, Kebriaei P, Shpall EJ, Giralt S, Champlin RE, Stastny P, Fernandez-Vina M. Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood. 2009 Oct 1;114(14):2884-7. doi: 10.1182/blood-2009-05-223172. Epub 2009 Aug 4.
PubMed 19654407
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation
- ClinicalTrials.gov ID
- NCT00506922
- Acronym / sponsor ID
- ID00-132
- Keywords
- Graft-Versus-Host Disease, GVHD Prevention, Hodgkin's Disease, Leukemia, Lymphoma, Methotrexate, Tacrolimus, Pentostatin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc.
- Study start
- Sep 2000
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 25 Jul 2007 (estimated)
- Results
- Posted 28 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation.
Secondary Objectives:
- To determine safety of escalating doses of pentostatin in combination with tacrolimus and methotrexate.
- To reduce the incidence of acute GVHD following transplants with unrelated donor to 40%.
- To document blood levels of tacrolimus when combined with pentostatin.
Detailed description
During the study, patients will have blood, urine, bone marrow, and X-ray exams done. These exams are done to monitor the results of the transplantation. Blood tests will be done daily while patients are hospitalized.
Patients in this study will receive chemotherapy and/or radiation to treat their malignancy and prevent graft rejection. This is given before the infusion of donor cells.
Patients with myeloid leukemias may receive busulfan by vein (IV) for 4 days and cyclophosphamide by vein for 2 days.
Patients with lymphoid malignancies may receive thiotepa by vein in one dose, cyclophosphamide by vein for 2 days, and irradiation for 4 days.
Other chemotherapy treatments may be used before donor cell infusion.
IV injections will be given through a previously inserted catheter that extends into the vena cava (a large chest vein).
Patients will be randomly picked (as in the toss of a coin) to receive one of five different treatments. This is done to learn the benefit of pentostatin treatment and the appropriate dose. Four of the treatments will use different dose schedules of pentostatin. The fifth treatment group will receive no pentostatin at all. All patients receive tacrolimus and methotrexate.
Pentostatin will be given by vein in 4 doses during the first month after transplant. Tacrolimus (FK506) will be given by vein or mouth for 6 months. Methotrexate will be given by vein for 3 doses in the first week after transplant.
Patients will receive blood and platelet transfusions after the transplant. The number of transfusions will depend on how quickly the blood cell counts return to a normal range.
Patients will remain in the hospital for about 4-6 weeks and in the Houston area for 100 days after the transplant.
This is an investigational study. All of the study drugs are commercially available. Pentostatin will not be used for GVHD prevention outside of this study. A total of 150 patients will take part in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| No Pentostatin | Experimental | Drug: Pentostatin, Drug: Tacrolimus, Drug: MethotrexateGroup 1: No Pentostatin |
| Pentostatin 0.5 | Experimental | Drug: Pentostatin, Drug: Tacrolimus, Drug: MethotrexateGroup 2: Pentostatin 0.5 mg/m^2 |
| Pentostatin 1 | Experimental | Drug: Pentostatin, Drug: Tacrolimus, Drug: MethotrexateGroup 3: Pentostatin 1 mg/m^2 |
| Pentostatin 1.5 | Experimental | Drug: Pentostatin, Drug: Tacrolimus, Drug: MethotrexateGroup 4: Pentostatin 1.5 mg/m^2 |
| Pentostatin 2 | Experimental | Drug: Pentostatin, Drug: Tacrolimus, Drug: MethotrexateGroup 5: Pentostatin 2 mg/m^2 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.
- Patients with AML, ALL, Hodgkin's disease, MDS (including CMML), CML in late chronic or accelerated phase or in blast crisis, and lymphoma in first or later relapses.
- Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.
- Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.
Key exclusion criteria (5 listed)
- HIV seropositivity
- Uncontrolled infection
- Pregnancy
- Candidates should not have received chemotherapy other than hydroxyurea or Gleevec for at least 3 weeks prior to treatment. Maintenance therapy with oral chemotherapy is acceptable. Treatment day is defined as transplant day +8, which is the date of first dose of pentostatin.
- Diagnosis of myelofibrosis.
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 |
|---|---|---|
| PentostatinAlso: Nipent, Deoxycoformycin, DCFGiven intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2 | Drug | No Pentostatin, Pentostatin 0.5, Pentostatin 1, Pentostatin 1.5, Pentostatin 2 |
| TacrolimusAlso: PrografGiven intravenously from day -2, and will be switched to oral dosing when tolerated. | Drug | No Pentostatin, Pentostatin 0.5, Pentostatin 1, Pentostatin 1.5, Pentostatin 2 |
| MethotrexateGiven intravenously on days +1, +3, and +6 at the dose of 5 mg/m2. | Drug | No Pentostatin, Pentostatin 0.5, Pentostatin 1, Pentostatin 1.5, Pentostatin 2 |
Primary outcome
Number of Patients Without GVHD at 100 Days
Time frame: 100 days
The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19654407Parmar S, Del Lima M, Zou Y, Patah PA, Liu P, Cano P, Rondon G, Pesoa S, de Padua Silva L, Qazilbash MH, Hosing C, Popat U, Kebriaei P, Shpall EJ, Giralt S, Champlin RE, Stastny P, Fernandez-Vina M. Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood. 2009 Oct 1;114(14):2884-7. doi: 10.1182/blood-2009-05-223172. Epub 2009 Aug 4.
- UT MD Anderson Cancer Center websiteLink 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.
Marcos de Lima, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pentostatin, Tacrolimus and Methotrexate in people with Leukemia and Lymphoma, run by M.D. Anderson Cancer Center 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 4 inclusion and 5 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 28 Apr 2015. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Mar 2011). 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?
Number of Patients Without GVHD at 100 Days (time frame: 100 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00506922, which also lists 1 linked publication.
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 28 Apr 2015.