Gene Therapy for Fanconi Anemia

NCT ID: NCT01331018

Last Updated: 2024-05-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-22

Study Completion Date

2024-02-15

Brief Summary

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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.

Detailed Description

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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

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Fanconi Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (hematopoietic stem progenitor cells)

STEM 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.

Group Type EXPERIMENTAL

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow harvest

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Genetically Engineered Hematopoietic Stem Progenitor Cells

Intervention Type BIOLOGICAL

Undergo infusion of genetically modified hematopoietic progenitor cell therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Leukapheresis

Intervention Type PROCEDURE

Undergo leukapheresis

Methylprednisolone

Intervention Type DRUG

Given IV

Plerixafor

Intervention Type DRUG

Given SC

Prednisone

Intervention Type DRUG

Given PO

Interventions

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Bone Marrow Aspiration

Undergo bone marrow harvest

Intervention Type PROCEDURE

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Genetically Engineered Hematopoietic Stem Progenitor Cells

Undergo infusion of genetically modified hematopoietic progenitor cell therapy

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Leukapheresis

Undergo leukapheresis

Intervention Type PROCEDURE

Methylprednisolone

Given IV

Intervention Type DRUG

Plerixafor

Given SC

Intervention Type DRUG

Prednisone

Given PO

Intervention Type DRUG

Other Intervention Names

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FILGRASTIM, LICENSE HOLDER UNSPECIFIED G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim Genetically Engineered HSPCs Leukocytopheresis Therapeutic Leukopheresis Adlone Caberdelta M DepMedalone Depo Moderin Depo-Nisolone Duralone Emmetipi Esametone Firmacort Medlone 21 Medrate Medrol Medrol Veriderm Medrone Mega-Star Meprolone Methylprednisolonum Metilbetasone Solubile Metrocort Metypresol Metysolon Predni-M-Tablinen Prednilen Radilem Sieropresol Solpredone Summicort Urbason Veriderm Medrol Wyacort AMD 3100 JM-3100 Mozobil SDZ SID 791 .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone

Eligibility Criteria

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Inclusion Criteria

* 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
* 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%

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Rocket Pharma Limited

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hans-Peter Kiem

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-00202

Identifier Type: REGISTRY

Identifier Source: secondary_id

RG9212015

Identifier Type: OTHER

Identifier Source: secondary_id

2097.00

Identifier Type: -

Identifier Source: org_study_id

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