Haploidentical Donor Hematopoietic Stem Cell Transplant in Treating Patients With Hematologic Malignancies
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
Studie Overzicht
Toestand
Conditie
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19107
- Thomas Jefferson University
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Any patient with a hematologic or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
- Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
Patients must have adequate organ function:
- LVEF (Left ventricular ejection fraction) of >50%
- Diffusion Capacity for Carbon Monoxide (DLCO) >50% of predicted corrected for hemoglobin
- Adequate liver function as defined by a serum bilirubin <1.8, Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
- Creatinine clearance of > 60 ml/min
- Performance status > 80% (TJU Karnofsky)
- Hematopoietic Comorbidity Index (HCT-CI) Score < 5 Points
- Patients must be willing to use contraception if they have childbearing potential
- Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent
Exclusion Criteria:
- Performance status < 80 % (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 < 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 anti-thymocyte globulin and have an ATG level of > 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: 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. |
IV gegeven
Andere namen:
IV gegeven
Andere namen:
IV gegeven
Andere namen:
Undergo TBI
Andere namen:
Undergo DLI
Andere namen:
Undergo haploidentical allogeneic HSCT
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Number of Participants With Disease-free Survival (DFS)
Tijdsspanne: 1 year
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Disease free survival (DFS), defined as the time to death, relapse or disease progression.
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1 year
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Number of Participants With Relapse of Disease
Tijdsspanne: Up to 1 year
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Relapse of Disease is defined as the return of a disease or the signs and symptoms of a disease after a period of improvement.
Relapse is almost always associated with the immunological failure of the donor immune system to recognize and/or respond to reemergence of a tumor.
The number of participants with relapse of disease will be collected.
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Up to 1 year
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Rate of Grade III-IV GVHD in Female Recipients With Male Donors
Tijdsspanne: Up to 1 year
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The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals.
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Up to 1 year
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The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals.
Tijdsspanne: Up to 1 year
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The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test.
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Up to 1 year
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Medewerkers en onderzoekers
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Enzymremmers
- Antireumatische middelen
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Antibacteriële middelen
- Antibiotica, antineoplastiek
- Antituberculeuze middelen
- Antibiotica, antituberculair
- Calcineurineremmers
- Cyclofosfamide
- Tacrolimus
- Mycofenolzuur
Andere studie-ID-nummers
- 13D.127
- 2012-104 (Andere identificatie: CCRRC)
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