Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor

NCT01350245 | Completed Phase 2 Results DMC

• 3 other identifiers: 10D.2192010-10JT 2150
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The primary hypothesis of this research study is that patients in remission undergoing myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS) rate at 1 year that is the same or better than the historical DFS of patients with similar diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS rate of 50% or better at 1 year would meet the criterion for an effective alternative therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach over T-replete matched sibling HSCT.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia; Hematopoietic stem cell transplant (HSCT); myeloablative haploidentical HSCT; graft versus host disease (GVHD)

Outcome Measures

Primary Outcomes (2)

• Disease-Free Survival (DFS)

  1-year post-transplant disease free survival (DFS), defined as success if a patient is alive and disease free at 1-year post-transplant.

  1 year post-transplant

• Probability of Overall Survival at 15 Months Post-treatment

  Probability of overall survival at 15 months post-treatment, defined as success if a patient is alive 1-year post-transplant.

  15 months

Study Arms (1)

TJU 2 Step Regimen

EXPERIMENTAL

All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone.

Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus; Device: Hematopoietic stem cell transplantation (HSCT)

Interventions

Total Body Irradiation (TBI) RADIATION

Total body irradiation is given in 8 fractions over 4 days (total dose of 12 Gy).

TJU 2 Step Regimen

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.

TJU 2 Step Regimen

Cyclophosphamide DRUG

Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days

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

TJU 2 Step Regimen

Mycophenolate Mofetil (MMF) DRUG

Started the day before the transplant to prevent graft versus host disease (GVHD)

Also known as: CellCept

TJU 2 Step Regimen

Tacrolimus DRUG

Started the day before the transplant to prevent graft-versus-host disease (GVHD)

Also known as: FK-506, Fujimycin

TJU 2 Step Regimen

Hematopoietic stem cell transplantation (HSCT) DEVICE

One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-donor stem cell product. This is the day of transplant. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

Also known as: CliniMACS

TJU 2 Step Regimen

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 without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
• Diagnoses include:
• Acute Myeloid Leukemia Myelodysplastic Syndromes Biphenotypic Leukemia Acute Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Lymphocytic Leukemia Plasma Cell Neoplasms Lymphoma Hodgkin Disease Aplastic Anemia
• Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
• Patients must adequate organ function:
• LVEF of \> or = 50%
• DLCO \> or = 50% of predicted corrected for hemoglobin
• Adequate liver function as defined by a serum bilirubin \< or = 1.8, AST or ALT \< or = 2.5X upper limit of normal
• Creatinine clearance of \> or = 60 ml/min
• Performance status \> or = 70% (TJU Karnofsky)
• HCT-CI Score \< 5 Points
• Patients must be willing to use contraception if they have childbearing potential
• Able to give informed consent

You may not qualify if:

• Performance status \< or = 70% (TJU Karnofsky)
• HCT-CI Score \> 5 Points
• Combination of Performance status of \< 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.
• 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 \< or = 6 months for reasons other than their underlying hematologic/oncologic disorder
• Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of \> or = 2 ugm/ml
• Patients who cannot receive cyclophosphamide
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms, Plasma Cell; Lymphoma; Hodgkin Disease; Anemia, Aplastic; Graft vs Host Disease

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dolores Grosso, CRNP, DNP
• Organization: Thomas Jefferson University

Dolores.Grosso@jefferson.edu

215-955-8874

Study Officials

• Dolores Grosso, DNP, CRNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 9, 2011
• Study Start: July 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: May 16, 2025
• Results First Posted: October 13, 2014

Record last verified: 2025-05

Locations

US (1)