Gene Therapy for Fanconi Anemia

NCT01331018 | Terminated Phase 1 DMC

• 3 other identifiers: 2097.00NCI-2011-00202RG9212015
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fanconi Anemia

Outcome Measures

Primary Outcomes (4)

• Toxicity of gene transfer

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

  Up to 15 years

• Hematological and non-hematological organ toxicity

  Adverse events will be graded by CTCAE, version 4.

  Up to 15 years

• Development of insertional mutagenesis or hematologic malignancy

  Adverse events will be graded by CTCAE, version 4.

  Up to 15 years

• Development of replication competent lentivirus

  Adverse events will be graded by CTCAE, version 4.

  Up to 15 years

Secondary Outcomes (6)

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

  Up to 6 days

• Efficacy of lineage depletion of bone marrow or mobilized cell product

  Up to 15 years

• Transduction efficiency

  Day 0

• Detectable levels of transduced cells in blood and marrow

  Up to 1 year

• Improved blood counts

  Up to 15 years

Study Arms (1)

Treatment (hematopoietic stem progenitor cells)

EXPERIMENTAL

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.

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

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow harvest

Treatment (hematopoietic stem progenitor cells)

Filgrastim BIOLOGICAL

Given SC

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (hematopoietic stem progenitor cells)

Genetically Engineered Hematopoietic Stem Progenitor Cells BIOLOGICAL

Undergo infusion of genetically modified hematopoietic progenitor cell therapy

Also known as: Genetically Engineered HSPCs

Treatment (hematopoietic stem progenitor cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (hematopoietic stem progenitor cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (hematopoietic stem progenitor cells)

Methylprednisolone DRUG

Given IV

Also known as: 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

Treatment (hematopoietic stem progenitor cells)

Plerixafor DRUG

Given SC

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791

Treatment (hematopoietic stem progenitor cells)

Prednisone DRUG

Given PO

Also known as: .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

Treatment (hematopoietic stem progenitor cells)

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Rocket Pharma Limited: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Leukapheresis; Methylprednisolone; exifone; Medrol Veriderm; plerixafor; ferric pyrophosphate; Prednisone; deltacortene; prednylidene

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Hans-Peter Kiem

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2011
• First Posted: April 7, 2011
• Study Start: February 22, 2012
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

US (1)