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

NCT03480360 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: D17170NCI-2018-01157
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Myelodysplasia; Myeloproliferative Disorder; Myelofibrosis; Lymphoma; Lymphoma, Non-Hodgkin; Plasma Cell Disorder; Acute Myeloid Leukemia; Chronic Myeloid Leukemia

Keywords

haploidentical; transplant; peripheral blood; allogeneic

Outcome Measures

Primary Outcomes (10)

• Number of Participants Who Survived to 100-Days Post-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.

  Define one year survival of subjects

  One year post date of peripheral blood transplant

• Number of Participants Who Experienced a Successful Engraftment

  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

  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

  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

  Define subjects who experienced toxicities associated with this treatment regimen

  Post-peripheral blood transplant

• Number of Participants Who Had Incidence of Acute GVHD

  Define subjects who had incidence of acute GVHD

  Post-peripheral blood transplant

• Number of Participants Who Had Incidence of Chronic GVHD

  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.

  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

  Define subjects who experienced treatment-related mortality within the first 100 days post-peripheral blood transplant

  100 days post-peripheral blood transplant

Secondary Outcomes (7)

• Immune Checkpoint Regulators - Incidence

  Days 30, 60, and 90 post-transplant

• Myeloid-derived Suppressor Cells (MDSCs) After Graft vs. Host Disease (GVHD) Diagnosis - Checkpoint Regulator Expression

  Post-transplant through study completion or death, assessed up to 3 years post-transplant

• MDSCs After GVHD Diagnosis - Peripheral Blood Mononuclear Cells

  Post-transplant through study completion or death, assessed up to 3 years post-transplant

• MDSCs After GVHD Diagnosis - Myeloid Subsets Using Flow Cytometry

  Post-transplant through study completion or death, assessed up to 3 years post-transplant

• MDSCs After GVHD Diagnosis - Frequency

  Post-transplant through study completion or death, assessed up to 3 years post-transplant

Study Arms (1)

Johns Hopkins' conditioning regimen

OTHER

Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant

Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Drug: Tacrolimus; Drug: cellcept; Drug: g-csf; Procedure: Peripheral Blood Transplant

Interventions

Cyclophosphamide DRUG

14.5 mg/kg for 2 days (days -6, -5) and then 50 mg/kg for two days (days 3, 4)

Johns Hopkins' conditioning regimen

Fludarabine DRUG

30 mg/m2 daily for 5 days

Johns Hopkins' conditioning regimen

Total Body Irradiation RADIATION

200 centigray (cGy) for one day (day -1)

Johns Hopkins' conditioning regimen

Tacrolimus DRUG

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.

Johns Hopkins' conditioning regimen

cellcept DRUG

dose at 15 mg/kg po three times per day (maximum dose of 3 grams/day). Stop Cellcept at Day 35 following transplantation.

Johns Hopkins' conditioning regimen

g-csf DRUG

5 mcg/kg/d starting day 5 and continue until Absolute Neutrophil Count (ANC) \> 1000/mcL for 3 days.

Johns Hopkins' conditioning regimen

Peripheral Blood Transplant PROCEDURE

cell dose goal: \< 5 x 106 Hematopoietic progenitor cell antigen CD34+ cells/kg recipient weight

Johns Hopkins' conditioning regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (23)

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Refractory, with Excess of Blasts; Myeloproliferative Disorders; Primary Myelofibrosis; Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell

Interventions

Cyclophosphamide; fludarabine; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Kenneth Meehan, MD
• Organization: Dartmouth-Hitchcock Medical Center

Kenneth.R.Meehan@hitchcock.org

(603) 650-4628

Study Officials

• Kenneth Meehan, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investogator- Kenneth Meehan, MD Staff Physician

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: March 29, 2018
• Study Start: March 28, 2018
• Primary Completion: February 14, 2025
• Study Completion (Estimated): October 17, 2026
• Last Updated: February 19, 2026
• Results First Posted: July 23, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)