Haploidentical Donor Hematopoietic Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT ID: NCT01871441

Last Updated: 2025-05-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-17

Study Completion Date

2016-10-20

Brief Summary

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This phase II trial studies how well haploidentical donor hematopoietic stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may replace the patient's immune cells and help destroy any remaining cancer cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Detailed Description

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PRIMARY OBJECTIVES:

I. Examine the 1 year disease free survival (DFS) rate of patients with maternal donors or sibling donors who share the maternal haplotype (maternal group) and compare them to patients receiving cells from donors who have points from other characteristics such as killer immunoglobulin-like receptor (KIR) ligand mismatching, minor histocompatibility antigen (MHag) differences, or number of human leukocyte antigen (HLA) mismatches (non-maternal group).

SECONDARY OBJECTIVES:

I. Assess the incidences of relapse and graft-versus-host disease (GVHD) in maternal recipients whose only eligible donors are offspring.

II. Assess the incidence of grades III-IV GVHD in female recipients with male donors.

III. Compare the rates of DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch.

OUTLINE:

Patients undergo total body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.

TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.

After completion of study treatment, patients are followed up at 90, 180, and 270 days, and 1 year.

Conditions

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Malignant Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (haploidentical allogeneic HSCT)

Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.

Group Type EXPERIMENTAL

Total-body irradiation

Intervention Type RADIATION

Undergo TBI

Donor lymphocytes infusion (DLI)

Intervention Type BIOLOGICAL

Undergo DLI

Cyclophosphamide

Intervention Type DRUG

Given IV

Allogeneic hematopoietic stem cell transplantation (HSCT)

Intervention Type PROCEDURE

Undergo haploidentical allogeneic HSCT

Tacrolimus

Intervention Type DRUG

Given IV

Mycophenolate mofetil

Intervention Type DRUG

Given IV

Interventions

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Total-body irradiation

Undergo TBI

Intervention Type RADIATION

Donor lymphocytes infusion (DLI)

Undergo DLI

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Allogeneic hematopoietic stem cell transplantation (HSCT)

Undergo haploidentical allogeneic HSCT

Intervention Type PROCEDURE

Tacrolimus

Given IV

Intervention Type DRUG

Mycophenolate mofetil

Given IV

Intervention Type DRUG

Other Intervention Names

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TBI Allogeneic Lymphocytes ALLOLYMPH Endoxan Cytoxan Neosar Procytox Revimmune cytophosphane FK-506 fujimycin Prograf Advagraf Protopic CellCept Myfortic MMF

Eligibility Criteria

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Inclusion Criteria

1. Any patient with a hematologic or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
3. Patients must have adequate organ function:

1. LVEF (Left ventricular ejection fraction) of \>50%
2. Diffusion Capacity for Carbon Monoxide (DLCO) \>50% of predicted corrected for hemoglobin
3. Adequate liver function as defined by a serum bilirubin \<1.8, Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5X upper limit of normal
4. Creatinine clearance of \> 60 ml/min
4. Performance status \> 80% (TJU Karnofsky)
5. Hematopoietic Comorbidity Index (HCT-CI) Score \< 5 Points
6. Patients must be willing to use contraception if they have childbearing potential
7. Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent

Exclusion Criteria

1. Performance status \< 80 % (TJU Karnofsky)
2. HCT-CI Score \> 5 Points
3. Combination of Performance status of \< 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.
4. HIV positive
5. Active involvement of the central nervous system with malignancy
6. Psychiatric disorder that would preclude patients from signing an informed consent
7. Pregnancy
8. Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder
9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an ATG level of \> 2 ugm/ml
10. Patients who cannot receive cyclophosphamide
11. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sidney Kimmel Cancer Center at Thomas Jefferson University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dolores Grosso, DNP, CRNP

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

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Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Related Links

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http://www.JeffersonHospital.org

Thomas Jefferson University Hospitals

Other Identifiers

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2012-104

Identifier Type: OTHER

Identifier Source: secondary_id

JT 3048

Identifier Type: OTHER

Identifier Source: secondary_id

13D.127

Identifier Type: -

Identifier Source: org_study_id

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