Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02833805
Other study ID # J1688
Secondary ID IRB00107139
Status Completed
Phase Phase 2
First received
Last updated
Start date September 2016
Est. completion date July 2021

Study information

Verified date June 2022
Source Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.


Description:

This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.


Recruitment information / eligibility

Status Completed
Enrollment 21
Est. completion date July 2021
Est. primary completion date July 2021
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA) - One of the following available donors: 1. HLA-haploidentical relative 2. If recipient is >= 40 years old, may use HLA-matched related donor 3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor - Recipient and/or legal guardian must sign protocol informed consent - Donor must be willing to donate bone marrow - Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead. - Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age - For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight - For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2. - For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50% - For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air - Karnofsky/Lansky status (depending on age) >= 70% - Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence. Exclusion Criteria: - Previous administration of immunosuppressive therapy for SAA. - Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old. - Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination - Presence of anti-donor antibodies - Prior allogeneic stem cell transplant - Prior solid organ transplant - Uncontrolled bacterial, viral, or fungal infection - HIV seropositivity - Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT) - Pregnancy or active breastfeeding - Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.

Study Design


Intervention

Drug:
Thymoglobulin
Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily
Fludarabine
Days -6 through -2: 30 mg/m^2 IV daily
Cyclophosphamide
Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
Radiation:
Total body irradiation
Day -1: 200 centigray (cGy) in a single fraction
Drug:
Tacrolimus
Start on Day 5 through Day 365
Mycophenolate mofetil
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Locations

Country Name City State
United States Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland

Sponsors (1)

Lead Sponsor Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival and Engraftment at One Year Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT). 1 year
Secondary Overall Survival at One Year Number of participants alive at one year after BMT. 1 year
Secondary Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC). 1 year
Secondary Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year. 1 year
Secondary Number of Participants Who Experience Primary Graft Failure Number of participants who experience primary graft failure by one year after BMT. 1 year
Secondary Number of Participants Who Experience Secondary Graft Failure Number of participants who experience secondary graft failure by one year after BMT. 1 year
Secondary Number of Participants Who Experience Grades II-IV Acute GVHD Number of participants who experience grade II, III, or IV acute GVHD by Day 100. Day 100
Secondary Number of Participants Who Experience Grades III-IV Acute GVHD Number of participants who experience grade III or IV acute GVHD by Day 100. Day 100
Secondary Number of Participants Who Experience Chronic GVHD Number of participants who experience chronic GVHD by two years after BMT. 2 years
Secondary Number of Participants With Full Donor Chimerism Number of participants with full donor chimerism at Day 60. Day 60
Secondary GVHD-free Relapse-free Survival (GRFS) Number of participants alive, without relapse, and without GVHD at 1 year. 1 year
Secondary Transplant-related Mortality Number of participants deceased for reasons related to BMT at 1 year. 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT05060991 - Impact of Immunosuppression Adjustment on COVID-19 Vaccination Response in Kidney Transplant Recipients Phase 4
Completed NCT01252537 - Immunosuppression in HIV-infected Patients With Tuberculosis in Ethiopia N/A
Completed NCT01678937 - Immune Tolerance and Alloreactivity in Liver Transplant Recipients on Different Monotherapy Immunosuppressive Agents N/A
Completed NCT00621699 - Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects Phase 1
Completed NCT00788021 - Protective Immunity Project 01 N/A
Active, not recruiting NCT00166842 - Sirolimus Blood Concentrations on Conversion From Oral Solution to Tablets Phase 4
Recruiting NCT05616130 - Pathological Myeloid Activation After Sepsis and Trauma
Completed NCT03117192 - Zinc Supplementation on Cellular Immunity in Thalassemia Major Phase 4
Recruiting NCT01568697 - Oral Bacteria and Immune System Problems Involved in Gum Disease (Periodontitis)
Not yet recruiting NCT06024226 - Role of MDSCs and Cancer Stem Cells and Their Cross Talks in NSCLC
Not yet recruiting NCT04961229 - Booster Dose of COVID-19 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response Phase 4
Completed NCT03139565 - High Dose vs. Standard Influenza Vaccine in Adult SOT Phase 3
Completed NCT02547753 - Dental Extractions Among Renal Transplant Recipients
Completed NCT01702207 - Evaluation Of Switching From Twice Daily Tacrolimus To Once Daily Formulation On Cardiovascular Risk Phase 4
Completed NCT00626808 - A Post Marketing Evaluation of the Effectiveness of FluMist Risk Minimization Plan in Children Phase 4
Completed NCT00419575 - Renal Transplantation With Immune Monitoring N/A
Completed NCT00783380 - Influenza Vaccination in Immunocompromized Patients Phase 4
Completed NCT04835948 - Efficacy of Single Dose Anti-thymocyte Globulin in the Modulation of T Lymphocytes in Kidney Transplantation
Recruiting NCT05043870 - Combined Immunosuppression for Pediatric Crohn's Disease Phase 4
Recruiting NCT05537948 - Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients Phase 4