Chronic Myeloproliferative DisordersPhase 1/2NCT00089037

Sirolimus, Tacrolimus, and Methotrexate in Preventing Acute Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplantation

A Phase 1/2 study testing methotrexate, sirolimus and tacrolimus in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

RATIONALE: Sirolimus, tacrolimus, and methotrexate may be effective in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation. PURPOSE: This phase I/II trial is studying the side effects of sirolimus when given together with tacrolimus and methotrexate and to see how… Read more about this study

Who is it for?: Any age
Conditions the study is for: Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia
What is being tested?: methotrexate, sirolimus and tacrolimus
How many people: Not given
Where: 1 siteUnited States
Study dates: Jun 2003to Apr 2005
Phase: Phase 1/2

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

DISEASE CHARACTERISTICS:

Diagnosis of hematological malignancy
No chronic phase chronic myelogenous leukemia, de novo acute leukemia in first remission, or myelodysplastic syndromes with refractory anemia
Scheduled for hematopoietic stem cell transplantation from unrelated donors
Currently receiving conditioning regimen comprising cyclosporine and total body radiotherapy (1,200 to 1,350 cGy) or busulfan and cyclosporine
Donor must be typed to the highest level of resolution
One single non-serologic disparity for A, B, or C alleles allowed provided the disparity is within the third or fourth digit of the allele
No mismatch at DRB1 or DQB1

PATIENT CHARACTERISTICS:

Age

Per primary treatment protocol

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

SGOT and SGPT ≤ 2.0 times upper limit of normal
Bilirubin normal
Hepatitis B and C virus negative

Renal

Creatinine clearance ≥ 70 mL/min

Cardiovascular

No cardiac insufficiency requiring treatment
No coronary artery disease

Pulmonary

No acute pulmonary infection by chest x-ray
No severe hypoxemia with pO_2 < 70 mm Hg AND DLCO < 70% of predicted
No mild hypoxemia with pO_2 < 80 mm Hg AND DLCO < 60% of predicted

Other

Not pregnant or nursing
Negative pregnancy test
HIV negative
No active systemic infection
No known hypersensitivity to macrolide antibiotics (e.g., erythromycin, azithromycin, or clarithromycin)
No prior intolerance or unresponsiveness to sirolimus

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No concurrent T-cell depleted transplantations

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics

Surgery

Not specified

Other

No concurrent grapefruit juice
No concurrent voriconazole

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024

Other trials in United States

About this study

Official title: A Phase I/II Study of Sirolimus in Addition to Tacrolimus and Methotrexate for the Prevention of Acute-Graft-Versus-Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplantation From Unrelated Donors

RATIONALE: Sirolimus, tacrolimus, and methotrexate may be effective in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation.

PURPOSE: This phase I/II trial is studying the side effects of sirolimus when given together with tacrolimus and methotrexate and to see how well they work in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation for hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

Determine the safety and efficacy of sirolimus when administered with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation from unrelated donors.

Secondary

Determine the absorption and pharmacokinetics of sirolimus in patients treated with this regimen.
Correlate sirolimus blood concentration with prevention of GVHD or toxicity in patients treated with this regimen.
Determine the severity of post-transplantation mucositis in patients treated with this regimen.

OUTLINE: This is a nonrandomized, open-label, pilot study.

Patients receive oral sirolimus once daily on days -3 to 175 and tacrolimus IV continuously beginning on day -3 and continuing until the patient is able to tolerate food and then orally twice daily until day 175. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Treatment continues in the absence of acute graft-vs-host disease or unacceptable toxicity.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3 years.

Conditions: Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Being tested: methotrexate, sirolimus, tacrolimus
Keywords: graft versus host disease, accelerated phase chronic myelogenous leukemia, atypical chronic myeloid leukemia, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, de novo myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent adult Burkitt lymphoma
Medical subject headings: Myeloproliferative Disorders, Graft vs Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2003Apr 2005

First posted5 Aug 2004 (estimated)
Study startJun 2003
Primary completionApr 2005
Study completionApr 2005

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
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: Supportive care
Masking: None (open label)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00089037
Sponsor's protocol ID: 1811.00
Other IDs: FHCRC-1811.00, CDR0000378004
Status last verified: Jul 2011
First submitted: 4 Aug 2004
Last updated: 15 Jul 2011
Results posted: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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