A Two-Step Approach to Bone Marrow Transplant Using Cells From A Partially-Matched Relative

NCT00429143 | Completed Phase 1 Results DMC

• 3 other identifiers: 06U.202005-84JT 1157
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to develop a way of treating patients who do not have a completely matched family donor or a readily available unrelated donor with bone marrow transplant by using a partially-matched family donor. Patients receiving this type of transplant will receive chemotherapy and/or radiation to treat their disease. They will also receive their donor's cells in 2 parts. During the first part, the donor's lymphocytes will be exposed to one of the chemotherapy agents to help the patient become tolerant to the lymphocytes. In the second part of the transplant, the patient will receive their donor's stem cells to help recover their peripheral blood counts and establish long-term engraftment. The hypothesis of this study is that in partially-matched allogeneic transplant, there is a defined number of donor T-cells that can be treated and given to the recipient to avoid post-transplant infection without causing severe graft-versus-host disease.

Conditions

Hematologic Malignancies

Keywords

Hematologic Malignancies; Two Step Approach; Haploidentical Transplant

Outcome Measures

Primary Outcomes (2)

• Overall Survival of Participants

  To determine overall survival at 6 months post-transplant.

  6 months

• Optimal Dose of CD3+ Donor Lymphocytes (T-cells) for Consistent Engraftment Without GVHD

  To determine the optimal dose of CD3+ donor lymphocytes required for consistent engraftment without the development of grade III/IV GVHD. Measured as CD3+ donor lymphocytes given as n x 10\^8/kg. "n" was found to be 2 and was found to be the optimal dose and was the only dose given.

  6 months

Secondary Outcomes (3)

• Engraftment Rates

  6 months

• Lymphoid Recovery

  6 months

• Incidence of Grades III-IV GVHD

  6 months

Study Arms (1)

Haploidentical Allogeneic Transplantation

EXPERIMENTAL

Patients undergoing hematopoietic stem cell transplant from a partially matched related donor

Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide (CY); Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Biological: Hematopoietic Stem Cell Transplant (HSCT)

Interventions

Total Body Irradiation (TBI) RADIATION

TBI twice daily days 6-9 prior to transplant (HSCT)

Also known as: TBI, radiotherapy

Haploidentical Allogeneic Transplantation

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

DLI given 6 days prior to transplant (HSCT).

Also known as: DLI, T cell infusion

Haploidentical Allogeneic Transplantation

Cyclophosphamide (CY) DRUG

Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).

Also known as: CY, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Haploidentical Allogeneic Transplantation

Tacrolimus DRUG

Tacrolimus given one day prior to transplant (HSCT).

Also known as: FK-506, fujimycin, Prograf, Advagraf, Protopic

Haploidentical Allogeneic Transplantation

Mycophenolate Mofetil (MMF) DRUG

MMF given one day prior to transplant (HSCT).

Also known as: MMF, CellCept, Myfortic

Haploidentical Allogeneic Transplantation

Hematopoietic Stem Cell Transplant (HSCT) BIOLOGICAL

CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.

Also known as: HSCT, stem cell transplant

Haploidentical Allogeneic Transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied.
• Patients must have a related donor who is either a one, two or three out of six antigen mismatch at the HLA-A;B;DR loci.
• Patients without a well-matched unrelated donor or those who have a disease status that precludes a wait for an identified unrelated donor.
• Patients must adequate organ function:
• LVEF of \>45%
• FVC or FEV1 \>45% of predicted
• Adequate liver function as defined by a serum bilirubin \<1.8, AST or ALT \< 2.5X upper limit of normal
• Serum creatinine \< 2.0 mg/dl or creatinine clearance of \> 40 ml/min
• Performance status \> 60% (Karnofsky)
• Patients must be willing to use contraception if they have childbearing potential
• Able to give informed consent

You may not qualify if:

• An eligible HLA-identical sibling donor.
• Performance status \< 60% (Karnosfsky)
• HIV positive
• Active involvement of the central nervous system with malignancy
• Psychiatric disorder that would preclude patients from signing an informed consent
• Pregnancy
• Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Grosso D, Carabasi M, Filicko-O'Hara J, Kasner M, Wagner JL, Colombe B, Cornett Farley P, O'Hara W, Flomenberg P, Werner-Wasik M, Brunner J, Mookerjee B, Hyslop T, Weiss M, Flomenberg N. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011 Oct 27;118(17):4732-9. doi: 10.1182/blood-2011-07-365338. Epub 2011 Aug 25.

  PMID: 21868572 DERIVED

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Whole-Body Irradiation; Radiotherapy; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Limitations of the trial include small sample size and single institution

Results Point of Contact

• Title: Neal Flomenberg, MD
• Organization: Thomas Jefferson University

neal.flomenberg@jefferson.edu

215-955-4367

Study Officials

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2007
• First Posted: January 31, 2007
• Study Start: January 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: June 1, 2010
• Last Updated: May 4, 2025
• Results First Posted: May 31, 2013

Record last verified: 2025-05

Locations

US (1)