Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00968630
First received: August 28, 2009
Last updated: May 28, 2014
Last verified: May 2014

August 28, 2009
May 28, 2014
December 2009
September 2016   (final data collection date for primary outcome measure)
  • Quantification of donor-derived HIV-1-specific immune responses following HCT [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    HIV-1 specific immune responses will be evaluated in samples collected before and after HCT. These results will be used descriptively.
  • Quantification of latently infected CD4+ cells in HIV+ patients [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    The overall measure of efficacy will be the log change in HIV-1 latent reservoir, measured as infectious units per million.
  • Quantification of HIV-1-specific immune response [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Quantification of latent HIV reservoir [ Time Frame: One year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00968630 on ClinicalTrials.gov Archive Site
  • Number of participants who die from HIV-associated mortality [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Analyzed descriptively.
  • Feasibility of continuous HAART after conditioning, defined by number of days off HAART [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Analyzed descriptively.
  • Feasibility of controlling HIV-1 replication post-HCT, defined by number of days without evidence of HIV-1 messenger (m)RNA (viral load) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Analyzed descriptively.
  • HIV-associated mortality [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Feasibility of continuous HAART after conditioning [ Time Frame: Number of days off HAART ] [ Designated as safety issue: Yes ]
  • Feasibility of controlling HIV-1 replication post-HCT [ Time Frame: Number of days without evidence of HIV-1 mRNA (viral load) ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer
Human Immunodeficiency Virus (HIV)-Specific Immune Reconstitution After Hematopoietic Cell Transplant for Treatment of Hematologic Malignancy in Patients Infected With HIV

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.

PRIMARY OBJECTIVES:

I. 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. 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. Determine mortality caused by HIV-related events following HCT in HIV+ patients.

II. Determine feasibility of continuous highly active antiretroviral therapy (HAART) administration after conditioning, defined by number of days off 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, and then annually thereafter as feasible. 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • 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)
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • B-cell Adult Acute Lymphoblastic Leukemia
  • B-cell Childhood Acute Lymphoblastic Leukemia
  • B-cell Chronic Lymphocytic Leukemia
  • 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
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • HIV Infection
  • HIV-associated Hodgkin Lymphoma
  • Intraocular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Previously Treated Myelodysplastic Syndromes
  • 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 Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin 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 Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Myelodysplastic Syndromes
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Adult Acute Lymphoblastic Leukemia
  • T-cell Childhood Acute Lymphoblastic Leukemia
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • 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:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Other: laboratory biomarker analysis
    Correlative studies
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, +365, and +730, and then annually thereafter as feasible. 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.
Interventions:
  • Procedure: leukapheresis
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: autologous hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
Not Provided
September 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age < 66 years for autologous recipients; ages < 76 for allogeneic recipients
  • 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 chronic myeloid leukemia (CML), or unclassified myeloproliferative disorders
    • Hodgkin 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; eligibility criteria for patients enrolled at other institutions may be determined by the Institutional Primary Research protocol in lieu of criteria listed above
  • 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 upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
  • Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) 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; exclusion criteria for patients enrolled at other institutions may be determined by the Institutional Primary Research protocol in lieu of that listed above
  • 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
Both
up to 75 Years
No
United States
 
NCT00968630
2212.00, NCI-2009-01244, 2212.00, P30CA015704, U19AI096111, P01CA018029
Yes
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • National Cancer Institute (NCI)
Principal Investigator: Ann Woolfrey Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP