Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

City of Hope

Status

Active, not recruiting

Conditions

Stage I Mycosis Fungoides/Sezary Syndrome

Stage III Mantle Cell Lymphoma

Polycythemia Vera

Stage IV Marginal Zone Lymphoma

Cutaneous B-cell Non-Hodgkin Lymphoma

Chronic Neutrophilic Leukemia

T-cell Large Granular Lymphocyte Leukemia

Hematopoietic/Lymphoid Cancer

Noncontiguous Stage II Grade 1 Follicular Lymphoma

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Noncontiguous Stage II Mantle Cell Lymphoma

Stage II Adult T-cell Leukemia/Lymphoma

Recurrent Grade 3 Follicular Lymphoma

Recurrent Marginal Zone Lymphoma

Stage III Grade 3 Follicular Lymphoma

Post-transplant Lymphoproliferative Disorder

Progressive Hairy Cell Leukemia, Initial Treatment

Recurrent Grade 1 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Stage I Multiple Myeloma

Contiguous Stage II Adult Lymphoblastic Lymphoma

Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma

Angioimmunoblastic T-cell Lymphoma

Chronic Myelomonocytic Leukemia

Noncontiguous Stage II Small Lymphocytic Lymphoma

Stage III Adult Diffuse Mixed Cell Lymphoma

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Stage III Adult Diffuse Large Cell Lymphoma

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Stage III Adult Burkitt Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Stage III Adult Diffuse Small Cleaved Cell Lymphoma

Stage II Mycosis Fungoides/Sezary Syndrome

Stage III Multiple Myeloma

Stage III Marginal Zone Lymphoma

Refractory Hairy Cell Leukemia

Stage II Cutaneous T-cell Non-Hodgkin Lymphoma

Contiguous Stage II Grade 1 Follicular Lymphoma

Stage I Grade 2 Follicular Lymphoma

Refractory Multiple Myeloma

Stage IV Adult Diffuse Mixed Cell Lymphoma

Stage IV Adult T-cell Leukemia/Lymphoma

Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma

Stage I Cutaneous T-cell Non-Hodgkin Lymphoma

Stage IV Adult Hodgkin Lymphoma

Stage I Adult Hodgkin Lymphoma

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Adult Immunoblastic Large Cell Lymphoma

Stage III Mycosis Fungoides/Sezary Syndrome

Recurrent Adult Lymphoblastic Lymphoma

Stage I Grade 1 Follicular Lymphoma

Stage III Small Lymphocytic Lymphoma

Aplastic Anemia

Contiguous Stage II Grade 3 Follicular Lymphoma

Stage IV Adult Diffuse Large Cell Lymphoma

Noncontiguous Stage II Grade 2 Follicular Lymphoma

Stage III Cutaneous T-cell Non-Hodgkin Lymphoma

Stage IV Adult Immunoblastic Large Cell Lymphoma

Contiguous Stage II Adult Diffuse Large Cell Lymphoma

Stage II Chronic Lymphocytic Leukemia

Stage III Adult T-cell Leukemia/Lymphoma

Secondary Myelodysplastic Syndromes

Stage IV Adult Burkitt Lymphoma

Stage IV Chronic Lymphocytic Leukemia

Stage I Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Acute Myeloid Leukemia

Acute Undifferentiated Leukemia

Stage II Multiple Myeloma

Stage IV Small Lymphocytic Lymphoma

Stage I Marginal Zone Lymphoma

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Stage IV Adult Diffuse Small Cleaved Cell Lymphoma

Chronic Eosinophilic Leukemia

Splenic Marginal Zone Lymphoma

Adult Acute Myeloid Leukemia in Remission

Noncontiguous Stage II Marginal Zone Lymphoma

Contiguous Stage II Adult Burkitt Lymphoma

Stage I Small Lymphocytic Lymphoma

Adult Grade III Lymphomatoid Granulomatosis

Cytomegalovirus Infection

Recurrent Adult Grade III Lymphomatoid Granulomatosis

Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma

Stage IV Adult Lymphoblastic Lymphoma

Blastic Phase Chronic Myelogenous Leukemia

Stage III Chronic Lymphocytic Leukemia

Essential Thrombocythemia

Primary Systemic Amyloidosis

Stage I Adult Diffuse Mixed Cell Lymphoma

Stage III Adult Immunoblastic Large Cell Lymphoma

Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma

Recurrent Small Lymphocytic Lymphoma

Stage I Adult Burkitt Lymphoma

Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma

Stage III Adult Hodgkin Lymphoma

Stage I Adult Lymphoblastic Lymphoma

Accelerated Phase Chronic Myelogenous Leukemia

Stage III Adult Lymphoblastic Lymphoma

Nodal Marginal Zone B-cell Lymphoma

Noncontiguous Stage II Adult Lymphoblastic Lymphoma

Recurrent Adult Burkitt Lymphoma

Stage I Adult Diffuse Small Cleaved Cell Lymphoma

Contiguous Stage II Marginal Zone Lymphoma

Secondary Myelofibrosis

Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma

Recurrent Mycosis Fungoides/Sezary Syndrome

Adult Nasal Type Extranodal NK/T-cell Lymphoma

Chronic Phase Chronic Myelogenous Leukemia

Noncontiguous Stage II Adult Burkitt Lymphoma

Stage I Grade 3 Follicular Lymphoma

Stage III Grade 1 Follicular Lymphoma

Stage I Mantle Cell Lymphoma

Stage III Grade 2 Follicular Lymphoma

Waldenstrom Macroglobulinemia

Recurrent Adult Hodgkin Lymphoma

Stage IV Grade 2 Follicular Lymphoma

Contiguous Stage II Mantle Cell Lymphoma

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Stage I Chronic Lymphocytic Leukemia

Stage 0 Chronic Lymphocytic Leukemia

Anaplastic Large Cell Lymphoma

Previously Treated Myelodysplastic Syndromes

Isolated Plasmacytoma of Bone

Relapsing Chronic Myelogenous Leukemia

Recurrent Adult Diffuse Mixed Cell Lymphoma

Refractory Chronic Lymphocytic Leukemia

Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Stage IV Grade 3 Follicular Lymphoma

Stage IV Mycosis Fungoides/Sezary Syndrome

Stage II Adult Hodgkin Lymphoma

Adult Acute Myeloid Leukemia With Del(5q)

Intraocular Lymphoma

Prolymphocytic Leukemia

Contiguous Stage II Small Lymphocytic Lymphoma

de Novo Myelodysplastic Syndromes

Meningeal Chronic Myelogenous Leukemia

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Recurrent Adult Diffuse Large Cell Lymphoma

Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma

Adult Acute Lymphoblastic Leukemia in Remission

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Contiguous Stage II Grade 2 Follicular Lymphoma

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Noncontiguous Stage II Grade 3 Follicular Lymphoma

Stage I Adult T-cell Leukemia/Lymphoma

Extramedullary Plasmacytoma

Stage IV Mantle Cell Lymphoma

Mast Cell Leukemia

Stage I Adult Diffuse Large Cell Lymphoma

Primary Myelofibrosis

Secondary Acute Myeloid Leukemia

Atypical Chronic Myeloid Leukemia, BCR-ABL Negative

Recurrent Adult T-cell Leukemia/Lymphoma

Stage IV Grade 1 Follicular Lymphoma

Treatments

Genetic: protein expression analysis

Other: flow cytometry

Genetic: DNA analysis

Procedure: antiviral therapy

Drug: ganciclovir

Procedure: management of therapy complications

Other: laboratory biomarker analysis

Drug: foscarnet sodium

Genetic: RNA analysis

Drug: valganciclovir

Genetic: polymerase chain reaction

Procedure: infection prophylaxis and management

Study type

Observational

Funder types

Other

NIH

Identifiers

NCT01199562

NCI-2010-01932

09038

Details and patient eligibility

About

RATIONALE: Infection prophylaxis and management may help prevent cytomegalovirus (CMV) infection caused by a stem cell transplant.

PURPOSE:This clinical trial studies infection prophylaxis and management in treating cytomegalovirus infection in patients with hematologic malignancies previously treated with donor stem cell transplant.

Full description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy and safety of a individualized strategy for cytomegalovirus (CMV) preemptive management, one that monitors CMV viral load and clinical markers of immunosuppression to optimize use of ganciclovir in recipients of allogeneic hematopoietic cell transplantation (HCT) who experience CMV reactivation.

SECONDARY OBJECTIVES:

I. To investigate how donor killer-cell immunoglobulin-like receptors (KIR) genes of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known, influence CMV reactivation-free survival after allogeneic HCT, independently of clinical risk factors such as onset of acute graft-versus-host disease.

II. To investigate whether markers of natural killer (NK) cell function correlate with a) KIR/ligand compound genotype and baseline or concurrent clinical factors and b) with history of CMV reactivation and anti-CMV therapy at the time of NK cell collection.

III. To investigate associations between NK cell recovery and antigen-specific T cell immune reconstruction.

OUTLINE: Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV deoxyribonucleic acid (DNA) quantitative polymerase chain reaction (Q-PCR) is negative. Patients may receive additional courses based on subsequent CMV reactivations.

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

Enrollment

153 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis: hematologic malignancies/disorders including aplastic anemia and myelodysplastic syndrome
Procedure: first allogeneic, T cell-replete transplantation of stem-cells from peripheral blood or bone marrow of an human leukocyte antigen (HLA) matched, unrelated or nonsyngeneic sibling donor
CMV seropositive donor and/or recipient
Performance level: must have already been determined to be eligible for HCT at City of Hope (COH)
Organ function requirements: The minimum organ function requirements should be the same as the requirements for HCT
Informed Consent: All patients must be capable of signing a written informed consent and no consent can be provided by a legal guardian

Exclusion criteria

The recipient had prior polymerase chain reaction (PCR) positive CMV infection in blood or organ-specific disease in the past 12 months
The source of hematopoietic stem cells is T-cell depleted
Concomitant anti-graft-versus-host disease (GVD) treatment includes in vivo T cell depletion
Recipient is human immunodeficiency virus (HIV)-1 positive
No prior allogeneic HCT (Allo HCT) (autologous HCT [Auto HCT] is allowed)

Trial design

Primary purpose

Supportive Care

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

153 participants in 1 patient group

Arm I

Description:

Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV DNA Q-PCR is negative. Patients may receive additional courses based on subsequent CMV reactivations.

Treatment: