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

This study is currently recruiting participants.
Verified April 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: April 14, 2014
Last verified: April 2014
  Purpose

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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
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:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 ULN 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00968630

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: John Zaia    626-256-4673      
Principal Investigator: John Zaia         
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         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ann Woolfrey Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
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: April 14, 2014
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 April 15, 2014