Overview

This trial is active, not recruiting.

Condition malignant neoplasm
Treatments total-body irradiation, donor lymphocytes infusion (dli), cyclophosphamide, allogeneic hematopoietic stem cell transplantation (hsct), tacrolimus, mycophenolate mofetil
Phase phase 2
Sponsor Sidney Kimmel Cancer Center at Thomas Jefferson University
Start date May 2013
End date June 2018
Trial size 4 participants
Trial identifier NCT01871441, 13D.127, 2012-104

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
total-body irradiation TBI
Undergo TBI
donor lymphocytes infusion (dli) Allogeneic Lymphocytes
Undergo DLI
cyclophosphamide Endoxan
Given IV
allogeneic hematopoietic stem cell transplantation (hsct)
Undergo haploidentical allogeneic HSCT
tacrolimus FK-506
Given IV
mycophenolate mofetil CellCept
Given IV

Primary Outcomes

Measure
Disease-free survival (DFS)
time frame: 1 year

Secondary Outcomes

Measure
Rate of relapse and GVHD in maternal recipients whose only eligible donors are offspring
time frame: Up to 1 year
Rate of grade III-IV GVHD in female recipients with male donors
time frame: Up to 1 year
The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals.
time frame: Up to 1 year

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Two Step Approach to Haploidentical Hematopoietic Stem Cell Transplantation for Patients in Remission From HLA Partially-Matched Related Donors-Effect of Maternal Donors on Outcomes
Principal investigator Dolores Grosso, DNP, CRNP
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Thomas Jefferson University.