NCT00578903

Brief Summary

Patients have been diagnosed with severe Aplastic Anemia that have not responded to treatment with immunosuppressive therapy (drugs that suppress the immune system, for example Steroids). The immune system is the system in the body that helps protect the body and fights bacterial, viral and fungal infections. Research studies have shown that patients with Aplastic Anemia have improved survival (may live longer) after receiving a HLA (Human Leukocyte Antigen) identical sibling (brother and sister) stem cell transplants. Patients who do not have matched siblings can undergo immunosuppressive therapy, which has also shown to improve outcome. Unfortunately patients who do not respond to immunosuppressive therapy usually die. The best chance of survival for these patients is an HLA matched unrelated or mismatched related stem cell transplant as described below. Stem cells are created in the bone marrow. They mature into different types of blood cells that people need including red blood cells which carry oxygen around the body, white blood cells which help fight infections, and platelets which help the blood to clot and prevent bleeding. For a matched unrelated stem cell transplant, stem cells are collected from a person (donor) who is not related to the patient but who has the same type of stem cells. For a mismatched related stem cell transplant, stem cells are collected from a donor who is related to the patient and whose stem cells are almost the same as those of the patient but not exactly. The patient then receives high dose chemotherapy. This chemotherapy kills the stem cells in the patient's bone marrow. Stem cells that have been collected from the donor are then given to the patient to replace the stem cells that have been killed. The major problems associated with these types of stem cell transplants are graft rejection (where the patient's immune system rejects the donor stem cells) and severe graft versus host disease (GVHD), where the donors stem cell reacts against the patient's tissues in the body.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2002

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2002

Completed
5.9 years until next milestone

First Submitted

Initial submission to the registry

December 19, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 21, 2007

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2012

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

October 11, 2013

Completed
Last Updated

April 22, 2016

Status Verified

March 1, 2016

Enrollment Period

10.4 years

First QC Date

December 19, 2007

Results QC Date

August 4, 2013

Last Update Submit

March 24, 2016

Conditions

Keywords

Severe Aplastic AnemiaSevere

Outcome Measures

Primary Outcomes (1)

  • Number of Subjects Alive at 100 Days Post Transplant

    100 days

Secondary Outcomes (5)

  • Number of Patients With Engraftment Rate at 100 Days Post Transplant

    100 days post transplant

  • Number of Patients With Acute GVHD at 100 Days Post Transplant

    100 days

  • Number of Patients With Chronic GVHD at 2 Years Post Transplant

    2 years

  • Number of Subjects Alive at 1 Year Post Transplant

    1 year

  • Number of Subjects Alive at 2 Years Post Transplant

    2 years

Study Arms (1)

Patients

EXPERIMENTAL

Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member. Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion

Drug: CytoxanDrug: CampathRadiation: Total Body Irradiation (TBI)Drug: FK-506Drug: MethotrexateProcedure: Stem cell infusion

Interventions

Cytoxan will be given at 50 mg/kg per dose for 4 successive days.

Also known as: Cyclophosphamide
Patients

Campath will be given at a dose of 3 mg for patients whose weight is between 5 and 15 kg; at a dose of 5 mg for patients whose weight is between 16 and 30 kg; and at a dose of 10 mg for patients whose weight is greater than 30 kg. The last dose of Campath should be 24 hours or more before stem cell infusion.

Also known as: alemtuzumab
Patients

TBI will be given at a dose of 200 cGy for 6/6 HLA match and at a dose of 400 cGy in two fractions of 200 cGy each for 5/6 HLA matched donor.

Also known as: Irradiation
Patients
FK-506DRUG

FK-506 will be given at a dose of 0.03 mg/kg/day via continuous infusion over 24 hours from 4pm on day -2 until engraftment or when patient is able to take by mouth (PO), then 0.03 mg/kg PO every 12 hours.

Also known as: Tacrolimus
Patients

Methotrexate will be administered on day +1, day +3, day +6 and day +11 at a dose of 5 mg/m2. The day +11 dose may be omitted at the discretion of the bone marrow transplant (BMT) in-patient attending physician.

Patients

Where possible patients will receive bone marrow. Marrow will be collected as per National Marrow Donor Program (NMDP) guidelines to provide a volume of 15-20 ml/kg of marrow and/or 2-4 X 10\^8 nucleated cells/kg. In case marrow cannot be collected, peripheral blood stem cell (PBSC) will be substituted. A minimum of 5-6 X 10\^6 CD 34+ cells/kg should be collected, with a target of 10 X 10\^6/kg.

Patients

Eligibility Criteria

Age1 Minute - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Diagnosis of Severe Aplastic Anemia (SAA) based on bone marrow aspirate and biopsy results.
  • Failure to respond to immunosuppressive therapy.
  • Lack of an Human Leukocyte Antigen (HLA) identical family member.
  • A 6/6 or 5/6 HLA matched unrelated donor or a 5/6 matched related donor available after high resolution HLA typing.
  • Age from birth to 60 years.

You may not qualify if:

  • Severe disease other than aplastic anemia that would limit the probability of survival during the graft procedure. Patients who present with active infection must be treated to maximally resolve this problem before beginning the conditioning regimen.
  • Human immunodeficiency virus (HIV) seropositive patients
  • Patients who have clonal cytogenetic abnormalities or a myelodysplastic syndrome.
  • Patient greater than 60 years of age.
  • Women who are pregnant or nursing.
  • Patients with active hepatitis
  • Patients with severe cardiac dysfunction defined as shortening fraction \< 25%.
  • Patients with severe renal dysfunction defined as creatinine clearance \< 40 ml/mim/1.73m2.
  • Patient with severe pulmonary dysfunction with forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) 40% of predicted or 3 standard deviations (SD) below normal.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Anemia, AplasticLymphoma, Follicular

Interventions

CyclophosphamideAlemtuzumabWhole-Body IrradiationRadiationTacrolimusMethotrexate

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersBone Marrow DiseasesLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsRadiotherapyTherapeuticsInvestigative TechniquesPhysical PhenomenaMacrolidesLactonesAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Kathryn Leung
Organization
Baylor College of Medicine

Study Officials

  • Kathryn Leung, MD

    Baylor College of Medicine

    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
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

December 19, 2007

First Posted

December 21, 2007

Study Start

February 1, 2002

Primary Completion

July 1, 2012

Study Completion

July 1, 2012

Last Updated

April 22, 2016

Results First Posted

October 11, 2013

Record last verified: 2016-03

Locations