Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression
The standard Johns Hopkins' regimen will be used in study subjects, with the use of donor peripheral blood stem cells, rather than marrow. Clinical outcomes will be defined while focusing efforts on immune reconstitution focusing on immune checkpoint regulators after a related haploidentical stem cell transplant.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
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|Eligible Ages||18 Years - 75 Years|
- - Age: less than 75 years.
- - The patient must be approved for transplant by the treating transplant physician.
- - Pre-transplant Evaluation of allogeneic recipient (Appendix).
- - The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant.
- - Acute leukemia - Acute Myeloid Leukemia, Acute Lymphocytic Leukemia.
- - Chronic leukemia - Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia.
- - Myelodysplasia.
- - Myeloproliferative disorder.
- - Myelofibrosis.
- - Lymphoma - Non-Hodgkin's Lymphoma or Hodgkin's disease.
- - Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia.
- - Donor availability- the patient must have an identified RELATED haplo-identical donor.
- - No Human Immunodeficiency Virus infection or active hepatitis B or C.
- - Eastern Cooperative Oncology Group performance status: 0-2.
- - Diffusing capacity of carbon monoxide (DLCO) greater than or equal to 40 % predicted.
- - Left ventricular ejection fraction greater than or equal to 40% - Serum bilirubin < 2x upper limit of normal; transaminases < 3x normal at the time of transplant.
- - No active or uncontrollable infection.
- - In female, a negative pregnancy test if experiencing menstrual periods.
- - No major organ dysfunction precluding transplantation.
- - No evidence of an active malignancy that would limit the patient's survival to less than 2 years.
- - Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- - Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- - History of refractory systemic infection.
- - Human leukocyte antigen (HLA) haplo-identical matched related.
- - The donor must be healthy and must be willing to serve as a donor, based on standard National Marrow Donor Program (NMDP) guidelines and DHMC SOP - Donor Evaluation (Appendix) - The donor must have no significant co-morbidities that would put the donor at marked increased risk.
- - There is no age restriction for the donor.
- - Informed consent must be signed by donor.
- - The NMDP guidelines for exclusion criteria will be used (Appendix).
- - Pregnant or lactating donor.
- - HIV or active Hep B or C in the donor.
- - Donor unfit to receive G-CSF and undergo apheresis.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Dartmouth-Hitchcock Medical Center|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Kenneth Meehan, MD|
|Principal Investigator Affiliation||Dartmouth-Hitchcock Medical Center|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Myelodysplasia, Myeloproliferative Disorder, Myelofibrosis, Lymphoma, Lymphoma, Non-Hodgkin, Plasma Cell Disorder|
We propose a clinical trial to define clinical endpoints, including engraftment, 100-day survival and one year survival (Objective #1). We will characterize the incidence, prevalence and function of immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). We will correlate these laboratory results with clinical outcomes and the incidence of GVHD. As an exploratory aim, in those patients experiencing GVHD and requiring treatment, we will define the frequency/expression of checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.
Other: Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Drug: - Cyclophosphamide
14.5 mg/kg for 2 days (days -6, -5) and then 50 mg/kg for two days (days 3, 4)
Drug: - Fludarabine
30 mg/m2 daily for 5 days
Radiation: - Total Body Irradiation
200 centigray (cGy) for one day (day -1)
Drug: - Tacrolimus
1 mg IV daily, (or the oral equivalent) adjusted to achieve a level between 5 and 15 ng/ml. If there is no evidence of GVHD, discontinue Tacrolimus by Day 180.
Drug: - cellcept
dose at 15 mg/kg po three times per day (maximum dose of 3 grams/day). Stop Cellcept at Day 35 following transplantation.
Drug: - g-csf
5 mcg/kg/d starting day 5 and continue until Absolute Neutrophil Count (ANC) > 1000/mcL for 3 days.
Procedure: - Peripheral Blood Transplant
cell dose goal: < 5 x 106 Hematopoietic progenitor cell antigen CD34+ cells/kg recipient weight
Contact a Trial Team
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Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756