Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer
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This phase II trial studies the immune response after stem cell transplant in human immunodeficiency virus (HIV)-positive patients with hematologic cancer. Studying samples of blood from HIV-positive patients with cancer in the laboratory may help doctors learn more about changes that occur in the immune system after stem cell transplant
Condition | Intervention | Phase |
---|---|---|
Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Nasal Type Extranodal NK/T-cell Lymphoma AIDS-related Diffuse Large Cell Lymphoma AIDS-related Diffuse Mixed Cell Lymphoma AIDS-related Diffuse Small Cleaved Cell Lymphoma AIDS-related Immunoblastic Large Cell Lymphoma AIDS-related Lymphoblastic Lymphoma AIDS-related Peripheral/Systemic Lymphoma AIDS-related Small Noncleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia de Novo Myelodysplastic Syndromes HIV-associated Hodgkin Lymphoma Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma 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 Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Secondary Myelodysplastic Syndromes |
Procedure: leukapheresis Procedure: allogeneic hematopoietic stem cell transplantation Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Other: laboratory biomarker analysis Other: DNA analysis Other: RNA analysis Other: flow cytometry Other: reverse transcriptase-polymerase chain reaction Other: nucleic acid sequencing Other: protein expression analysis |
Phase 2 |
Study Type: | Interventional |
Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | Human Immunodeficiency Virus (HIV)-Specific Immune Reconstitution After Hematopoietic Cell Transplant for Treatment of Hematologic Malignancy in Patients Infected With HIV |
- Quantification of HIV-1-specific immune response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Quantitative plasma HIV RNA will be determined by a branched-chain DNA based assay and CD4+ and CD8+ T cell subsets will be evaluated by flow cytometry.
- Quantification of latent HIV reservoir [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Latent HIV will be detected in leukapheresis product using sensitive culture techniques and assessed by the log change in HIV-1 latent reservoir, measured as IUPM (infectious units per million).
- Number of participants who die from HIV-associated mortality [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
- Number of participants who receive continuous as opposed to disrupted HAART [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]Defined by number of days off HAART.
- Number of patients who have undetectable viral load after HCT [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Defined by number of days without evidence of HIV-1 mRNA (viral load).
Estimated Enrollment: | 10 |
Study Start Date: | December 2009 |
Estimated Primary Completion Date: | September 2016 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: Treatment (HIV-specific immune reconstitution after HCT)
Patients undergo leukapheresis for analysis of HIV-1 latent reservoir at baseline and at days +90, +180, and +365. Patients receive conditioning regimen, undergo either allogeneic or autologous marrow or peripheral blood stem cell transplantation, and receive graft-vs-host disease prophylaxis according to standard medical procedures. Patients undergo blood sample collection periodically for biomarker analysis. |
Procedure: leukapheresis
Undergo leukapheresis
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic HSCT
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous HSCT
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
Other: laboratory biomarker analysis
correlative study
Other: DNA analysis
correlative study
Other: RNA analysis
correlative study
Other: flow cytometry
correlative study
Other: reverse transcriptase-polymerase chain reaction
correlative study
Other Name: RT-PCR
Other: nucleic acid sequencing
correlative study
Other Names:
Other: protein expression analysis
correlative study
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To examine the development of donor-derived HIV-1-specific immune response following hematopoietic cell transplant (HCT) for treatment of hematologic malignancy in HIV+ patients.
II. To examine the affect of HCT on the pool of latently infected cluster of differentiation (CD)4+ T cells in HIV+ patients given HCT for treatment of hematologic malignancy.
SECONDARY OBJECTIVES:
I. To determine mortality caused by HIV-related events following HCT in HIV+ patients.
II. To determine feasibility of continuous HAART administration after conditioning, defined by number of days off highly active antiretroviral therapy (HAART).
III. Examine control of HIV-1 replication after HCT, defined by number of days without evidence of HIV-1 messenger ribonucleic acid (mRNA) (viral load).
OUTLINE:
Patients undergo leukapheresis for analysis of HIV-1 latent reservoir at baseline and at days +90, +180, +365, and +730. Patients receive conditioning regimen, undergo either allogeneic or autologous marrow or peripheral blood stem cell transplantation, and receive graft-vs-host disease prophylaxis according to standard medical procedures. Patients undergo blood sample collection periodically for biomarker analysis.
Ages Eligible for Study: | up to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- HIV positive
- Treatment with HAART for at least 1 month
- Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy
Hematologic malignancy associated with a poor prognosis with medical therapy alone - diagnoses to be included:
- Acute Myeloid Leukemia in first remission, second remission, or relapse
- Acute Lymphoblastic Leukemia in first remission, second remission, or relapse
- Chronic Myeloid Leukemia in accelerated phase or blast phase. Chronic phase is allowed if patient has not achieved a cytogenetic remission or has developed unacceptable toxicity to medical therapy, such as tyrosine kinase inhibitor therapy
- Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
- Myeloproliferative disorders, including Chronic Myelomonocytic Leukemia (CMML), Agnogenic Myeloid Metaplasia with Myelofibrosis, Juvenile CML, or unclassified myeloproliferative disorders
- Hodgkin's Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference
- Non-Hodgkin Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference
- Approval for allogenic regimen given at Patient Care Conference
- Additional inclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional required inclusion criteria
- DONOR: Autologous peripheral blood with CD34+ cell dose of > 3.0 x 10^6 cells per kilogram recipient weight; autologous recipients are allowed to proceed to nonmyeloablative allogeneic HCT on protocol 1410
- DONOR: Related donor matched for at least 9 of 10 human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 alleles
- DONOR: Unrelated donor matched for at least 9 of 10 HLA-A, B, C, DRB1, and DQB1 alleles and willing to donate either marrow or peripheral blood stem cells; the acceptable level of the single mismatch is defined as an allele level mismatch at HLA-DRB1 or an antigen level mismatch at HLA-A, B, C, or DQB1
- DONOR: Donor inclusion criteria may be expanded in the case where the patient is also enrolled on a separate Institutional Review Board (IRB)-approved Primary Research Protocol; please refer to the Primary Research Protocol for Donor Inclusion Criteria
Exclusion Criteria:
- Positive serology for toxoplasma gondii AND requiring treatment or with evidence of active infection
- A medical history of noncompliance with HAART or medical therapy
- Serum creatinine > 2 times upper limit of normal (ULN)
- Serum bilirubin greater than 3 times the ULN unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the ULN, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome
- Forced vital capacity (FVC), forced expiratory volume (FEV)1 or diffusing capacity of the lung for carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
- Cardiac insufficiency or coronary artery disease requiring treatment
- Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
- Karnofsky performance score < 70
- Cardiac insufficiency or coronary artery disease requiring treatment
- Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
- Karnofsky performance score < 70
- Patients capable of conceiving a child and unwilling to use procedures to prevent conception
- Pregnancy or patients actively breastfeeding
- Additional exclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional exclusion criteria
- DONOR: HIV positive
- DONOR: Medical or psychological reason that would make donor procedure intolerable
- DONOR: Age > 75 years
- DONOR: Medical history, physical exam, or laboratory findings that indicate donation would entail excess risk to donor or patient; this includes, but is not limited to pregnancy, history of autoimmune disorder, thromboembolism, serious adverse reaction to anesthesia, current treatment with lithium or monoclonal antibodies or any experimental drug, laboratory findings of hemoglobinopathy, thrombocytopenia, or blood borne pathogens; any unrelated donor must have approval by the Donor Center after evaluation by history and physical
United States, Washington | |
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Recruiting |
Seattle, Washington, United States, 98109 | |
Contact: Ann E. Woolfrey 206-667-4453 | |
Principal Investigator: Ann E. Woolfrey |
Principal Investigator: | Ann Woolfrey | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
No publications provided
ClinicalTrials.gov Identifier: | NCT00968630 History of Changes |
Other Study ID Numbers: | 2212.00, NCI-2009-01244, P01CA018029, U19AI096111 |
Study First Received: | August 28, 2009 |
Last Updated: | November 21, 2012 |
Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome HIV Infections Blast Crisis Burkitt Lymphoma Neoplasms Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase |
Leukemia, Myelomonocytic, Chronic Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Myelodysplastic Syndromes Preleukemia Leukemia, Myelomonocytic, Acute Myeloproliferative Disorders Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, Large-Cell, Anaplastic |
ClinicalTrials.gov processed this record on February 21, 2013