Clinical trial NCT00361049: Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant
Official title: Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: graft versus host disease
unspecified adult solid tumor, protocol specific
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)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
poor prognosis metastatic gestational trophoblastic tumor
previously treated myelodysplastic syndromes
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
splenic marginal zone lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage II ovarian epithelial cancer
stage III adult Burkitt lymphoma
stage III adult Hodgkin 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 chronic lymphocytic leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III multiple myeloma
stage III ovarian epithelial cancer
stage III small lymphocytic lymphoma
stage III malignant testicular germ cell tumor
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV adult Burkitt lymphoma
stage IV adult Hodgkin 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 breast cancer
stage IV chronic lymphocytic leukemia
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV ovarian epithelial cancer
stage IV small lymphocytic lymphoma
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-08-07
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Donor mesenchymal stem cell infusion may be an effective treatment for acute or chronic graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This phase I trial is studying the side effects and best dose of donor mesenchymal stem cells in treating patients with acute or chronic graft-versus-host disease after undergoing a donor stem cell transplant.

Detailed description: OBJECTIVES:

Primary

* Determine the safety of donor mesenchymal stem cell (MSC) infusion in patients with acute or extensive chronic graft-vs-host disease (GVHD) after undergoing HLA-identical sibling donor stem cell transplant.

Secondary

* Describe the rates of complete and partial resolution of GVHD when MSCs are used in addition to the standard GVHD therapy.
* Determine inflammatory cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in blood of patients with acute GVHD prior to therapy and at 7 and 14 days post-MSC therapy.
* Determine if donor MSCs engraft in tissues inflamed by GVHD in patients who have undergone gender-mismatched transplantation.

OUTLINE: This is a multicenter, dose-escalation study of donor mesenchymal stem cells (MSC).

Within 72 hours after the initiation of medical therapy (e.g., corticosteroids, cyclosporine) for graft-vs-host disease, patients undergo donor MSC infusion over 10-15 minutes.

Cohorts of 3-6 patients receive escalating doses of donor MSCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood samples are obtained periodically and examined by immunoenzyme techniques for mixed lymphocyte reaction (as a surrogate marker for alloreactivity) and cytokine levels (TH1 \[i.e., interleukin (IL)-2 and interferon-gamma\], TH2 \[i.e., IL-10 and IL-4\], and inflammatory cytokines \[i.e., tumor necrosis factor-alpha and IL-1\]). Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Developed acute graft-vs-host disease (GVHD) of clinical grade II-IV or extensive chronic GVHD after undergoing HLA-identical sibling donor hematopoietic stem cell transplant for any indication, malignant or nonmalignant

  * Requires systemic immunosuppressive therapy with systemic corticosteroids (methylprednisone dose 2 mg/kg/day or equivalent) and concurrent cyclosporine or tacrolimus
* May have been enrolled on an institutional allogeneic stem cell transplant protocol using either ablative or nonmyeloablative preparative regimens
* No evidence of relapsed or progressive malignant disease at the time of GVHD

PATIENT CHARACTERISTICS:

* Not pregnant
* Negative pregnancy test
* Creatinine clearance ≥ 20 mL/min
* Oxygen saturation ≥ 90% on room air
* No severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support
* No uncontrolled hypertension or congestive heart failure, active angina pectoris requiring the use of nitrates, myocardial infarction within the past 6 months, or major ventricular arrhythmia or cardiac failure requiring active treatment
* No significant organ dysfunction
* No active severe infections, including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis

  * Fever without a source is allowed

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Safety
timeFrame: Monitored for 6 hours for infusion related toxicity. Temperature, blood pressure, pulse and O2 saturation will be measured at baseline and every 10 minutes x 2, every 30 minutes x 2, and every hour x 3.
Secondary outcomes:
measure: Complete and partial resolution of graft-vs-host disease (GVHD)
timeFrame: Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.
measure: Cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in patients with acute GVHD
timeFrame: Pre-transplant, at diagnosis, 7 and 14 days after MSC infusion
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Geauga Regional Hospital
state: Ohio
city: Cleveland
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Suburban Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Chagrin Highlands Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Southwest General Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Westlake Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
Study officials:
affiliation: Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
name: Hillard M. Lazarus, MD
role: PRINCIPAL_INVESTIGATOR
References: