Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03480360|
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : January 9, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Myelodysplasia Myeloproliferative Disorder Myelofibrosis Lymphoma Lymphoma, Non-Hodgkin Plasma Cell Disorder||Drug: Cyclophosphamide Drug: Fludarabine Radiation: Total Body Irradiation Drug: Tacrolimus Drug: cellcept Drug: g-csf Procedure: Peripheral Blood Transplant||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates Examining Checkpoint Immune Regulators' Expression|
|Actual Study Start Date :||March 28, 2018|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
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
14.5 mg/kg for 2 days (days -6, -5) and then 50 mg/kg for two days (days 3, 4)
30 mg/m2 daily for 5 days
Radiation: Total Body Irradiation
200 centigray (cGy) for one day (day -1)
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.
dose at 15 mg/kg po three times per day (maximum dose of 3 grams/day). Stop Cellcept at Day 35 following transplantation.
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
- 100-Day Survival [ Time Frame: 100 days post date of peripheral blood transplant ]Define 100-day survival of subjects
- Immune Checkpoint Regulators - Incidence [ Time Frame: Days 30, 60, and 90 post-transplant ]To characterize the incidence of immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation, cytotoxic T-lymphocyte-associated protein 4 [CTLA], Programmed cell death protein 1 [PD-1]) during early immune recovery following an allogeneic stem cell transplant.
- Myeloid-derived suppressor cells (MDSCs) after Graft vs. Host Disease (GVHD) diagnosis - checkpoint regulator expression [ Time Frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant ]In those patients experiencing GVHD, the study team will define the checkpoint regulator expression on MDSCs
- MDSCs after GVHD diagnosis - peripheral blood mononuclear cells [ Time Frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant ]In those patients experiencing GVHD, the study team will define the peripheral blood mononuclear cells and myeloid subsets.
- MDSCs after GVHD diagnosis - myeloid subsets using flow cytometry [ Time Frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant ]In those patients experiencing GVHD, the study team will define the myeloid subsets.
- MDSCs after GVHD diagnosis - frequency [ Time Frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant ]In those patients experiencing GVHD, the study team will define the MDSCs frequency.
- Immune Checkpoint Regulators - Prevalence [ Time Frame: Days 30, 60, and 90 post-transplant ]To characterize the prevalence of immune checkpoint regulators (VISTA, CTLA-4, PD-1) during early immune recovery following an allogeneic stem cell transplant.
- Immune Checkpoint Regulators - Function [ Time Frame: Days 30, 60, and 90 post-transplant ]Flow cytometry will be used to characterize the function of immune checkpoint regulators (VISTA, CTLA-4, PD-1) during early immune recovery following an allogeneic stem cell transplant.
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, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- Age: less than 75 years
- The patient must be approved for transplant by the treating transplant physician. This includes completion of their pre-transplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedure (SOP) (DHMC SOP - 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. The diseases include:
- Acute leukemia - Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
- Chronic leukemia - Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia
- Myeloproliferative disorder
- 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. (If there is any question, the PI can make a decision).
- 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
DONOR EXCLUSION CRITERIA
- The NMDP guidelines for exclusion criteria will be used (Appendix). In addition, the following donors are NOT eligible:
- Pregnant or lactating donor
- HIV or active Hep B or C in the donor
- Donor unfit to receive G-CSF and undergo apheresis
- A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480360
|Contact: Research Nurse||(800) firstname.lastname@example.org|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Research Nurse 800-639-6918 email@example.com|
|Contact: Sean Hobson (603) 653-3637 Sean.Hobson@Hitchcock.org|
|Principal Investigator:||Kenneth Meehan, MD||Dartmouth-Hitchcock Medical Center|
|Responsible Party:||Kenneth Meehan, Principal Investogator- Kenneth Meehan, MD Staff Physician, Dartmouth-Hitchcock Medical Center|
|Other Study ID Numbers:||
|First Posted:||March 29, 2018 Key Record Dates|
|Last Update Posted:||January 9, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Immune System Diseases
Bone Marrow Diseases
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating