Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression

January 30, 2026 updated by: Kenneth Meehan, Dartmouth-Hitchcock Medical Center

Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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
  • 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. (If there is any question, the PI can make a decision).

Exclusion Criteria:

  • 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

DONOR ELIGIBILITY

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Survived to 100-Days Post-transplant
Time Frame: 100 days post date of peripheral blood transplant
Define 100-day survival of subjects
100 days post date of peripheral blood transplant
Number of Participants Who Survived to One Year Post-Transplant.
Time Frame: One year post date of peripheral blood transplant
Define one year survival of subjects
One year post date of peripheral blood transplant
Number of Participants Who Experienced a Successful Engraftment
Time Frame: Post-peripheral blood transplant
Define number of subjects who experience a successful engraftment: Defined as absolute neutrophil count > 500/mm3 and platelets > 20,000/mcl for three consecutive days (count first day as engraftment)
Post-peripheral blood transplant
Number of Participants Who Achieved a Response to Treatment at 100 Days
Time Frame: 100 days post-peripheral blood transplant
Define response to treatment at 100 days post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
100 days post-peripheral blood transplant
Number of Participants Who Achieved a Response to Treatment at One Year
Time Frame: One year post-peripheral blood transplant
Define response to treatment at one year post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
One year post-peripheral blood transplant
Number of Participants Who Experienced Toxicities Associated With This Treatment Regimen
Time Frame: Post-peripheral blood transplant
Define subjects who experienced toxicities associated with this treatment regimen
Post-peripheral blood transplant
Number of Participants Who Had Incidence of Acute GVHD
Time Frame: Post-peripheral blood transplant
Define subjects who had incidence of acute GVHD
Post-peripheral blood transplant
Number of Participants Who Had Incidence of Chronic GVHD
Time Frame: Post-peripheral blood transplant
Define subjects who had incidence of chronic GVHD
Post-peripheral blood transplant
Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
Time Frame: Days 30, 60, and 90 post-peripheral blood transplant
Define subjects who experience donor-recipient chimerism following transplant at days 30, 60 and 90. All patients were assessed for donor-recipient chimerism at days 30, 60, and 90, but only one patient experienced chimerism. Day 90 for this patient is reported.
Days 30, 60, and 90 post-peripheral blood transplant
Number of Participants Who Experienced Treatment-Related Mortality Within the First 100 Days
Time Frame: 100 days post-peripheral blood transplant
Define subjects who experienced treatment-related mortality within the first 100 days post-peripheral blood transplant
100 days post-peripheral blood transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Days 30, 60, and 90 post-transplant
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.
Days 30, 60, and 90 post-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.
Days 30, 60, and 90 post-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
Post-transplant through study completion or death, assessed up to 3 years post-transplant
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.
Post-transplant through study completion or death, assessed up to 3 years post-transplant
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.
Post-transplant through study completion or death, assessed up to 3 years post-transplant
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.
Post-transplant through study completion or death, assessed up to 3 years post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Investigators

  • Principal Investigator: Kenneth Meehan, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2018

Primary Completion (Actual)

February 14, 2025

Study Completion (Estimated)

October 17, 2026

Study Registration Dates

First Submitted

January 8, 2018

First Submitted That Met QC Criteria

March 21, 2018

First Posted (Actual)

March 29, 2018

Study Record Updates

Last Update Posted (Actual)

February 19, 2026

Last Update Submitted That Met QC Criteria

January 30, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D17170
  • NCI-2018-01157 (Other Identifier: National Cancer Institute)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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