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
  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 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
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Other: laboratory biomarker 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:

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Chronic Myeloproliferative Disorders Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Peripheral T-cell Lymphoma Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia
U.S. FDA Resources

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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


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, +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.
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

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, 2212.00, P30CA015704, U19AI096111, P01CA018029
Study First Received: August 28, 2009
Last Updated: May 28, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Cell Transformation, Neoplastic
Leukemia, B-Cell
Neoplasms, Plasma Cell
Congenital Abnormalities
Acquired Immunodeficiency Syndrome
HIV Infections
Blast Crisis
Burkitt Lymphoma
Neoplasms
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid

ClinicalTrials.gov processed this record on August 20, 2014