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Fanconi AnemiaPhase 1NCT01331018

Gene Therapy for Fanconi Anemia

A Phase 1 study testing Bone Marrow Aspiration, Filgrastim and Genetically Engineered Hematopoietic Stem Progenitor Cells in people with Fanconi Anemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This clinical trial will access the toxicity and efficacy of infusion of gene modified cells for patients with Fanconi anemia (FA). Infusion of autologous patient blood stem cells that have been corrected in the laboratory by introduction of the normal gene may improve blood counts in patients with FA. Read more about this study

Who is it for?
Ages 4 years and older
Conditions the study is for
Fanconi Anemia
What is being tested?
Bone Marrow Aspiration, Filgrastim and Genetically Engineered Hematopoietic Stem Progenitor Cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
22 Feb 2012to 15 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • FA demonstrated by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane performed by a Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) approved laboratory
  • FA complementation group A as determined by somatic cell hybrids, molecular characterization, western blot analysis, acquisition of mitomycin C resistance after in vitro lentiviral transduction with a vector bearing the complementary deoxyribonucleic acid (cDNA) for Fanconi complementation group A, or other clinically certified method of complementation group analysis
  • Bone marrow analysis demonstrating normal cytogenetics, and no more than 5% of cells with a single clonal abnormality by fluorescence in situ hybridization (FISH) for myelodysplastic syndrome (MDS) panel within 3 months of stem cell collection
  • Signed informed consent by the patient or legally authorized representative
  • Absolute neutrophil count >= 0.5 x 10^9/L
  • Hemoglobin >= 8 g/dL
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  • Platelet count >= 20 x 10^9/L and able to achieve a platelet count of >= 50 x 10^9/L with transfusion support
  • Adequate hepatic function with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
  • Adequate renal function with creatinine (Cre) =< 1.5; if greater, then glomerular filtration rate (GFR) > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation
  • Adequate pulmonary function with corrected diffusion capacity of carbon monoxide (DLCO) > 50% in those for whom this study can be performed
  • For subjects < 17 years of age, Modified Lansky Play-Performance Score of >= 70%; for subjects 17 and older, Karnofsky score of >= 70%

Who cannot join

  • Non-hematopoietic malignancy where the expected survival is less than 2 years
  • Myelodysplastic syndrome as defined by World Health Organization (WHO) criteria
  • Acute myeloid leukemia as defined by WHO criteria
  • Pregnancy or lactation; females of childbearing potential and males who are admitted to the study will be advised that the study procedures and study drugs may be teratogenic, and they will be required to take adequate measures to prevent conception for the duration of the study
  • Concurrent enrollment in any other study using an investigational drug
  • Physical or emotional status that would prevent informed consent, protocol compliance, or adequate follow-up
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  • Patients for whom an human leukocyte antigen (HLA) matched sibling donor bone marrow transplant is being actively pursued will not be eligible for study until it is determined that no sibling donor is available or that a stem cell transplant is not feasible during the time the patient might be on study
  • No patient will be included in this study as an alternative to a clinically indicated HLA matched sibling donor stem cell transplant
  • If an HLA matched sibling donor is identified, but stem cell or marrow collection is not feasible (e.g., donor is in utero, is a newborn from whom cord blood was not collected, or is unable to undergo a donation procedure because of ill health), a patient may be included in the study at the discretion of the investigators
  • Significant associated diseases including documented human immunodeficiency virus (HIV) infection, uncontrolled hypertension (diastolic blood pressures > 95%ile for age), unstable angina, congestive heart failure (> New York [NY] class II), poorly controlled diabetes (hemoglobin A1c [Hgb A1c] > 7%), coronary angioplasty within 6 months, myocardial infarction within the last 6 months, or uncontrolled atrial or ventricular cardiac arrhythmia, abnormal coagulation, persistent abnormal urinalysis reflecting intrinsic renal disease
  • Active ongoing viral, bacterial, or fungal infection

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)

This clinical trial will access the toxicity and efficacy of infusion of gene modified cells for patients with Fanconi anemia (FA). Infusion of autologous patient blood stem cells that have been corrected in the laboratory by introduction of the normal gene may improve blood counts in patients with FA.

Read the detailed description

OUTLINE:

STEM CELL MOBILIZATION FOR CELL COLLECTION: Patients receive filgrastim subcutaneously (SC) twice daily (BID) for up to 6 days (on days 1-6 of mobilization). Patients receive plerixafor SC once daily (QD) on days 4-6 of mobilization. Peripheral blood stem cell (PBSC) count will be checked daily starting on day 4 of mobilization. Patients who have a PBSC count of >= 5 CD34+ cells/mcL will undergo up to 2 apheresis collections on consecutive days.

BONE MARROW HARVEST FOR CELL COLLECTION: Patients with inadequate PBSC counts undergo bone marrow harvest for collection of stem/progenitor cells.

REINFUSION: Patients receive methylprednisolone intravenously (IV) or prednisone orally (PO) on days -1 to 7 followed by a rapid taper over approximately 1 week and undergo reinfusion of genetically modified hematopoietic stem/progenitor cells on day 0.

After completion of study treatment, patients are followed up periodically for 15 years.

Conditions
Fanconi Anemia
Being tested
Bone Marrow Aspiration, Filgrastim, Genetically Engineered Hematopoietic Stem Progenitor Cells, Laboratory Biomarker Analysis, Leukapheresis
Medical subject headings
Fanconi Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow harvest

  • FilgrastimBiological

    Also called FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF

    Given SC

  • Genetically Engineered Hematopoietic Stem Progenitor CellsBiological

    Also called Genetically Engineered HSPCs

    Undergo infusion of genetically modified hematopoietic progenitor cell therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • MethylprednisoloneDrug

    Also called Adlone, Caberdelta M, DepMedalone, Depo Moderin

    Given IV

  • PlerixaforDrug

    Also called AMD 3100, JM-3100, Mozobil, SDZ SID 791

    Given SC

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

Study groups in NCT01331018
Study groupRoleWhat they receive
Treatment (hematopoietic stem progenitor cells)ExperimentalSTEM CELL MOBILIZATION FOR CELL COLLECTION: Patients receive filgrastim SC BID for up to 6 days (on days 1-6 of mobilization). Patients receive plerixafor SC QD on days 4-6 of mobilization. PBSC count will be checked daily starting on day 4 of mobilization. Patients who have a PBSC count of >= 5 CD34+ cells/mcL will undergo up to 2 apheresis collections on consecutive days. BONE MARROW HARVEST FOR CELL COLLECTION: Patients with inadequate PBSC counts undergo bone marrow harvest for collection of stem/progenitor cells. REINFUSION: Patients receive methylprednisolone IV or prednisone PO on days -1 to 7 followed by a rapid taper over approximately 1 week and undergo reinfusion of genetically modified hematopoietic stem/progenitor cells on day 0.
Receives: Procedure: Bone Marrow Aspiration; Biological: Filgrastim; Biological: Genetically Engineered Hematopoietic Stem Progenitor Cells; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Drug: Methylprednisolone; Drug: Plerixafor; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity of gene transfer

    Adverse events will be graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.

    Measured: Up to 15 years

  2. Hematological and non-hematological organ toxicity

    Adverse events will be graded by CTCAE, version 4.

    Measured: Up to 15 years

  3. Development of insertional mutagenesis or hematologic malignancy

    Adverse events will be graded by CTCAE, version 4.

    Measured: Up to 15 years

  4. Development of replication competent lentivirus

    Adverse events will be graded by CTCAE, version 4.

    Measured: Up to 15 years

Secondary outcomes (6)

  1. Efficacy of G-CSF and plerixafor mobilization in Fanconi anemia (FA) patients

    Measured: Up to 6 days

  2. Efficacy of lineage depletion of bone marrow or mobilized cell product

    Measured: Up to 15 years

  3. Transduction efficiency

    After completion of lentiviral transduction, the percent gene modified cells will be determined by molecular studies.

    Measured: Day 0

  4. Detectable levels of transduced cells in blood and marrow

    Blood and bone marrow samples will be assayed by real-time quantitative polymerase chain reaction.

    Measured: Up to 1 year

  5. Improved blood counts

    Complete blood counts will be monitored, initially weekly, then monthly during the first year, then quarterly during the 2nd year after infusion.

    Measured: Up to 15 years

  6. Demonstrable functional expression by growth of recipient cells in mitomycin C

    Blood and bone marrow cells will be assayed for viability of cultured cells and hematopoietic colonies in the presence of the chemotherapy drug and deoxyribonucleic acid crosslinking agent, mitomycin C.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2011 (estimated)
  2. Study start22 Feb 2012
  3. Primary completion15 Feb 2024
  4. Study completion15 Feb 2024

Why it stopped: Study ended early due to end of funding.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01331018
Sponsor's protocol ID
2097.00
Other IDs
NCI-2011-00202, RG9212015
Status last verified
May 2024
First submitted
16 Mar 2011
Last updated
17 May 2024
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bone Marrow Aspiration, Filgrastim and Genetically Engineered Hematopoietic Stem Progenitor Cells in people with Fanconi Anemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study ended early due to end of funding.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity of gene transfer (time frame: Up to 15 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01331018.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.

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