Clinical trial NCT00096096: Tacrolimus and Mycophenolate Mofetil in Preventing Acute Graft-Versus-Host Disease in Patients With Advanced Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplantation
Official title: A Phase II Study of the Combination of Tacrolimus and Mycophenolate Mofetil for the Prevention of Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: graft versus host disease
accelerated phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult Burkitt lymphoma
chronic idiopathic myelofibrosis
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent mantle cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult lymphoblastic lymphoma
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
adult acute lymphoblastic leukemia in remission
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
chronic myelomonocytic leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory hairy cell leukemia
juvenile myelomonocytic leukemia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
chronic phase chronic myelogenous leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
refractory chronic lymphocytic leukemia
refractory cytopenia with multilineage dysplasia
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
childhood acute lymphoblastic leukemia in remission
childhood chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
splenic marginal zone lymphoma
atypical chronic myeloid leukemia
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-11-09
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Tacrolimus and mycophenolate mofetil may be an effective treatment for graft-versus-host disease caused by donor stem cell transplantation.

PURPOSE: This phase II trial is studying how well giving tacrolimus together with mycophenolate mofetil works in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation for advanced hematologic cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy of tacrolimus and mycophenolate mofetil in preventing acute graft-vs-host disease in patients with advanced hematologic malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Secondary

* Determine the safety of this regimen in these patients.

OUTLINE: This is a non-randomized study.

Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 60 followed by a taper to day 180. Patients also receive mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-60 followed by a taper to day 180. Treatment is discontinued at day 180 in the absence of graft-vs-host disease.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 5-25 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following hematologic malignancies:

  * Acute myeloid leukemia beyond first complete remission (CR1)
  * Acute lymphoblastic leukemia beyond CR1
  * Chronic myelogenous leukemia in second chronic phase, accelerated phase, or blastic phase
  * Non-Hodgkin's lymphoma beyond CR2
  * Hodgkin's lymphoma beyond CR2
  * Multiple myeloma (any stage)
  * Myelodysplastic syndromes beyond refractory anemia (including chronic myelomonocytic leukemia)
  * Any refractory hematologic malignancy
* Advanced disease
* Scheduled for transplantation of mobilized allogeneic peripheral blood stem cells

  * Genotypically HLA-identical stem cell donor available

PATIENT CHARACTERISTICS:

Age

* 65 and under

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* SGOT and SGPT ≤ 2.0 times ULN

Renal

* Creatinine clearance ≥ 60 mL/min

Pulmonary

* No acute pulmonary infection by chest x-ray
* No severe hypoxemia (partial O_2 \< 70% of predicted) AND DLCO \< 70% of predicted
* No mild hypoxemia (partial O_2 \< 80% of predicted) AND DLCO \< 60% of predicted

Other

* Not pregnant or nursing
* Negative pregnancy test
* No active systemic infection not controlled with antimicrobial therapy
* HIV negative (HIV-1 or other virus)

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent T-cell depleted hematopoietic stem cell graft

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Primary outcomes:
measure: Efficacy
Secondary outcomes:
measure: Safety
measure: Area under the curve of plasma mycophenolic acid
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Richard Nash, MD
role: PRINCIPAL_INVESTIGATOR
References: