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Immune Reconstitution in Oncology Patients Following Autologous Stem Cell Transplant

Completed
Conditions
Solid Tumor
Brain Tumor
Lymphoma
Interventions
Other: Blood samples obtained
Registration Number
NCT01540175
Lead Sponsor
St. Jude Children's Research Hospital
Brief Summary

Autologous stem cell rescue is an established therapy in high risk neuroblastoma and relapsed Hodgkin's lymphoma and an experimental therapy in some other solid and brain tumors to facilitate the use of very intense chemotherapy beyond bone marrow tolerance. It is usually tolerated with acceptable toxicity and graft failure is practically not existent. But whereas immune reconstitution in allogeneic hematopoietic stem cell transplantation (HSCT) setting is widely studied, the investigators have no comprehensive data available in the autologous setting regarding recovery of the innate and adaptive immune system. However, observations in patients with autoimmune disease undergoing autologous HSCT suggest not an exact recovery of the patient's pre-transplant immune system but some re-education during reconstitution of immune function.

Also, recent developments of cancer-directed immunotherapy with monoclonal antibodies and immunocytokines rely on activity of the patient's own immune system via complement-mediated or antibody-dependent cellular cytotoxicity. These novel therapies are given either with or shortly after conventional chemotherapy. To find the optimal time point for administration of immunotherapy, it is important to know how and when immune effector cells recover after conventional myelosuppressive and/or immunosuppressive chemotherapy which are used in Induction regimens.

Researchers at St. Jude Children's Research Hospital want to study the research participant's immune profile once prior and at multiple set time points after autologous stem cell infusion during the recovery process. In a subset of participants the investigators want to study the recovery of lymphocyte subsets and function after one course of conventional chemotherapy preceding the high dose chemotherapy and autologous stem cell transplant. That way the investigators hope to learn about the pace and order of recovery and the functional capacity of different compartments of the immune system during reconstitution.

Detailed Description

Primary Objective:

* To describe the immune reconstitution of T cell-, B cell- and natural killer (NK) cell- compartment in patients undergoing autologous stem cell transplant as part of their treatment for a malignancy.

The design for this study will be a prospective, longitudinal observational study. Immune reconstitution will be measured in the course of autologous stem cell transplant using serial blood samples analyzed for cell counts, immune cell phenotyping (demonstrating the expression of specific receptors on the cell surface) and functional lymphocyte assays. These blood samples will be obtained once prior and at defined time points after stem cell infusion either while the research participant is hospitalized or during the scheduled clinic visit.

Immune recovery from conventional chemotherapy will be measured using serial blood samples analyzed for cell counts, immune cell phenotyping, and NK cell functional assays. These blood samples will be obtained once prior and at defined time points after completion of courses #1 and #4 of Induction chemotherapy while the research participant is hospitalized or during the scheduled clinic visit.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
Inclusion Criteria
  • Patients with solid tumors, brain tumors or lymphoma regardless of previously received cancer related therapies who are enrolled on a study protocol or treatment plan that includes or will likely include autologous stem cell transplant.
  • Patient age >0 to 21 years
Exclusion Criteria
  • Patient receiving an autologous transplant for a disease other than listed above.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ParticipantsBlood samples obtainedParticipants enrolled on the study will have blood samples obtained.
Primary Outcome Measures
NameTimeMethod
Change in the immune reconstitution of T cell, B cell, and NK cell compartment.Days 0, 14, 21, 28, week 8, and months 3, 6, 12, and 18 related to stem cell infusion.

The order and magnitude of recovery of the different subtypes of leukocytes will be summarized by descriptive statistics. The pattern of immune reconstitution will be evaluated using longitudinal approaches such as Mixed effect models or GEE approach and implement in SAS 9.2 using PROC MIXED or PROC GENMOD.

In addition, NK cell number, receptor and ligand genotype and phenotype and functional capacity will be compared at specific time points (28 days, 8 weeks and 6 months post autologous transplant) to the baseline values using paired one sample signed rank test.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

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