Leukemia, Lymphoma, MDS, Multiple Myeloma, Myelodysplastic/Myeloproliferative Diseases, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Conditions
Brief summary
RATIONALE: Antiviral drugs, such as ganciclovir, act against viruses. Giving ganciclovir by infusion and then by mouth may be effective treatment for cytomegalovirus that has become active after donor bone marrow transplant. PURPOSE: This phase II trial is studying how well giving ganciclovir by infusion and by mouth works in treating patients with cytomegalovirus after donor bone marrow transplant.
Detailed description
OBJECTIVES: * To determine the feasibility of using oral ganciclovir (GCV) following induction with intravenous GCV in the setting of cytomegalovirus (CMV) reactivation after bone marrow transplantation. OUTLINE: Blood cultures for cytomegalovirus (CMV) are obtained periodically after the planned bone marrow transplantation (BMT). Patients showing reactivation of CMV receive induction ganciclovir (GCV) IV twice a day on days 1-7. Patients then receive maintenance oral GCV three times a day for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection periodically during study for pharmacokinetic studies.
Interventions
DRUGGanciclovir
Following the first CMV-positive blood culture on day 21 or later, or the first two consecutive CMV-positive PCR tests on day 21 or later, 5mg/kg/bid x 7 days of Ganciclovir is given intravenously, followed by oral Ganciclovir 1000 mg tid 7 days per week x 5 weeks
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Undergoing allogeneic transplantation, including unrelated donor bone marrow transplantation (BMT) and/or allogeneic donor leukocyte infusion, for any indication * Patients or their donors must have had a positive pre-BMT cytomegalovirus (CMV) antibody titer as measured by enzyme-linked immunosorbent assay (ELISA) PATIENT CHARACTERISTICS: * Able to comply with study requirements
Exclusion criteria
* Signs or symptoms of documented CMV infection, including any positive CMV culture from any site and/or any suspected or documented CMV-associated clinical syndrome, at the time of study entry * History of symptomatic CMV-associated clinical syndrome PRIOR CONCURRENT THERAPY: * Receiving concurrent investigational antiviral agents PATIENT CHARACTERISTICS: * History of hypersensitivity to ganciclovir or acyclovir
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first ganciclovir positive test, after day 21 post-hematopoietic cell transplant | This will be measured by the number of the CMV+ participants with adverse events occurring when receiving oral GCV. |
| Observation of Cytomegalovirus (CMV) in Blood as Measured by Either Blood Culture or Polymerase Chain Reaction (PCR) During the Course of Antiviral Treatment | Twice Weekly after day 21 post-transplant | — |
| Compliance Rate Among Patients With CMV Reactivation | From first ganciclovir positive test to the end of the 6th week GCV therapy | CMV reactivation patients completed 6-week GCV therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Blood Culture at Day 21 or later -or- PCR Test at Day 21 or later | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | CMV Not Detected | 13 |
| Overall Study | Death | 12 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants |
| Age, Continuous | 41 years |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 36 | 14 / 25 |
| other Total, other adverse events | 32 / 32 | 0 / 0 |
| serious Total, serious adverse events | 0 / 32 | 0 / 0 |
Outcome results
Primary
Compliance Rate Among Patients With CMV Reactivation
CMV reactivation patients completed 6-week GCV therapy.
Time frame: From first ganciclovir positive test to the end of the 6th week GCV therapy
Population: Among the 36 patients with CMV reactivation, two patients are in-evaluable for compliance.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CMV Reactivation Patients With GCV | Compliance Rate Among Patients With CMV Reactivation | Compliance | 26 participants |
| CMV Reactivation Patients With GCV | Compliance Rate Among Patients With CMV Reactivation | No Compliance | 8 participants |
Primary
Number of Participants With Adverse Events
This will be measured by the number of the CMV+ participants with adverse events occurring when receiving oral GCV.
Time frame: From first ganciclovir positive test, after day 21 post-hematopoietic cell transplant
Population: Patients are treated with Intravenous Ganciclovir followed by Oral Ganciclovir on detection of CMV reactivation. Among the 36 patients with CMV reactivation, four patients' adverse event data are not available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemorrhage/bleeding w/ grade 3 or 4 thrombocytopni | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Haptoglobin | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemoglobin | 31 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemolysis | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Leukocytes | 22 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Lymphopenia | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Neutrophils/granulocytes | 12 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Platelets | 26 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | pRBCs | 17 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | aGVHD | 21 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Flushing | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hair Loss / Alopecia | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pigmentation Changes | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pruritus/Itching | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Rash/Desquamation | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Rash/Desquamation w GVHD | 19 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Wound Complication, Non-infection | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Cushingoid Appearance | 15 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Endocrine - Other | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Thyroid Function, Low (Hypothyroidism) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Anorexia | 15 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Constipation | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dehydration | 16 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Diarrhea | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Gastrointestinal - Other | 6 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Heartburn/Dyspepsia | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Vomiting | 14 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hematuria (in the absence of vaginal bleeding) | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemorrhage/bleeding w/o grade 3 or 4 thrombocytope | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemorrhage, pulmonary/upper respiratory | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hemorrhage/Bleeding - Other | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Petechiae/purpura | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Bilirubin with GVHD | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Febrile Neutropenia | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Infection - Bacterial | 13 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | AST, SGOT | 23 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Albumin, serum-low (hypoalbuminemia) | 25 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Alkaline phosphatase | 11 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Bilirubin (hyperbilirubinemia) | 8 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | CPK (creatine phosphokinase) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Calcium, serum-high (hypercalcemia) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Calcium, serum-low (hypocalcemia) | 20 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Cholesterol, serum-high (hypercholesteremia) | 23 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Creatinine | 20 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Glucose, serum-high (hyperglycemia) | 24 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Magnesium, serum-high (hypermagnesemia) | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Magnesium, serum-low (hypomagnesemia) | 27 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Metabolic/Laboratory - Other | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Phosphate, serum-low (hypophosphatemia) | 21 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Potassium, serum-high (hyperkalemia) | 7 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Potassium, serum-low (hypokalemia) | 16 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Proteinuria | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Sodium, serum-low (hyponatremia) | 15 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Uric acid, serum-high (hyperuricemia) | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Muscle weakness, generalized or specific area | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Musculoskeletal/Soft Tissue - Other | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Myositis (inflammation/damage of muscle) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Confusion | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dizziness | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Memory Impairment | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Mood Alteration | 11 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Neurology - Other | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Neuropathy: Motor | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Neuropathy: Sensory | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Speech Impairment | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | cGVHD | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Palpitations | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Supraventricular and nodal arrhythmia | 19 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Cardiac General - Other | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hypertension | 13 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hypotension | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Edema | 8 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | INR | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Fatigue | 21 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Fever | 10 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Insomnia | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Rigors/Chills | 6 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Sweating | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Weight loss | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Bruising | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Skin - Other | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dry Skin | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Diarrhea with GVHD | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dry mouth/Salivary Gland (Xerostomia) | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Esophagitis | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Flatulence | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Gastritis | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Mucositis/Stomatitis | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Nausea | 22 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Stomatitis/pharyngitis (Oral/Pharyngeal Mucositis) | 16 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Taste Alteration (Dysgeusia) | 5 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Infection - Other | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Infection w/ unknown ANC | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Infection - Fungal | 3 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Infection - Viral | 8 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Lymphatics | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | ALT, SGPT | 31 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Syncope | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Tremor | 12 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dry eye syndrome | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Ocular/Visual - Other | 4 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Ophthalmoplegia/diplopia (double vision) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pain | 25 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Adult Respiratory Distress Syndrome (ARDS) | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Cough | 7 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Dyspnea (shortness of breath) | 7 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Hypoxia | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pleural effusion (non-malignant) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pneumonitis/pulmonary infiltrates | 6 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Pulmonary/Upper Respiratory - Other | 2 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Urinary frequency/urgency | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Urinary retention (including neurogenic bladder) | 1 Participants |
| CMV Reactivation Patients With GCV | Number of Participants With Adverse Events | Thrombosis/thrombus/embolism | 1 Participants |
Primary
Observation of Cytomegalovirus (CMV) in Blood as Measured by Either Blood Culture or Polymerase Chain Reaction (PCR) During the Course of Antiviral Treatment
Time frame: Twice Weekly after day 21 post-transplant
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMV Reactivation Patients With GCV | Observation of Cytomegalovirus (CMV) in Blood as Measured by Either Blood Culture or Polymerase Chain Reaction (PCR) During the Course of Antiviral Treatment | CMV Reactivation | 36 Participants |
| CMV Reactivation Patients With GCV | Observation of Cytomegalovirus (CMV) in Blood as Measured by Either Blood Culture or Polymerase Chain Reaction (PCR) During the Course of Antiviral Treatment | No CMV Reactivation | 25 Participants |