Clinical trial NCT00064311: Ravuconazole in Preventing Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation
Official title: A Phase I-II Safety, Tolerability And Pharmacokinetic Study Of Ravuconazole For Prophylaxis Of Invasive Fungal Infections In Patients Undergoing Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Chronic Myeloproliferative Disorders
Gestational Trophoblastic Tumor
Infection
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Neuroblastoma
Ovarian Cancer
Testicular Germ Cell Tumor
Keywords: infection
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult Burkitt lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult Burkitt lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV mantle cell lymphoma
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory hairy cell leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
disseminated neuroblastoma
recurrent neuroblastoma
stage II ovarian epithelial cancer
recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage IIIA breast cancer
stage IIIB breast cancer
stage IV breast cancer
high risk metastatic gestational trophoblastic tumor
primary myelofibrosis
recurrent adult acute lymphoblastic leukemia
adult acute lymphoblastic leukemia in remission
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia in remission
secondary acute myeloid leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
stage IIIC breast cancer
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-09
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antifungals such as ravuconazole may be effective in preventing fungal infections in patients undergoing chemotherapy and stem cell transplantation.

PURPOSE: Phase I/II trial to study the effectiveness of ravuconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation.

Detailed description: OBJECTIVES:

* Determine the safety and tolerability of ravuconazole for the prevention of invasive fungal infections in patients undergoing non-myeloablative allogeneic hematopoietic stem cell transplantation.
* Determine the pharmacokinetics and efficacy of this drug, in terms of frequency of breakthrough fungal infections and requirement for empirical antifungal therapy, in these patients.
* Determine the effect of this drug on concurrently administered cyclosporine in these patients.
* Determine the pharmacokinetics of this drug with and without cyclosporine in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral ravuconazole once daily beginning within 48 hours of the chemotherapy preparative regimen and before the initiation of cyclosporine. Treatment continues until blood counts recover in the absence of unacceptable toxicity.

Cohorts of 8 patients receive escalating doses of ravuconazole until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 8 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Undergoing a non-myeloablative allogeneic hematopoietic stem cell transplantation
* Must be able to start prophylactic antifungal therapy within 48 hours of the transplantation chemotherapy preparative regimen and before the initiation of cyclosporine
* No diagnosis of deeply invasive fungal infection based on the MSG/EORTC criteria

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Bilirubin no greater than 5 times upper limit of normal (ULN)
* AST and ALT no greater than 5 times ULN
* Alkaline phosphatase no greater than 5 times ULN

Renal

* Not specified

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception during and for 4 weeks (12 weeks for males) after study participation
* Able to swallow oral medication
* Sufficient venous access
* No prior anaphylaxis attributed to the azole class of antifungals
* No concurrent medical condition that may create an unacceptable additional risk for the patient during study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics

Chemotherapy

* Not specified

Endocrine therapy

* No concurrent hormonal contraceptives

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* At least 2 weeks since other prior non-FDA approved investigational drugs
* No concurrent QTc prolonging medication (e.g., terfenadine, cisapride, quinidine, pimozide, or dofetilide)
* No concurrent rifampin
* No other concurrent experimental or systemic antifungal therapy
* No concurrent agents containing amphotericin B
* No other concurrent systemic azole or triazole antifungal agents
* No concurrent echinocandins
* Concurrent topical antifungals allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Thomas J. Walsh, MD
role: STUDY_CHAIR
References: