Gene Therapy for Fanconi Anemia
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01331018 |
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Recruitment Status :
Active, not recruiting
First Posted : April 7, 2011
Last Update Posted : July 11, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Fanconi Anemia | 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 | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 3 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA) |
| Actual Study Start Date : | February 22, 2012 |
| Estimated Primary Completion Date : | July 17, 2032 |
| Estimated Study Completion Date : | July 17, 2032 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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. |
Procedure: Bone Marrow Aspiration
Undergo bone marrow harvest Biological: Filgrastim Given SC
Other Names:
Biological: Genetically Engineered Hematopoietic Stem Progenitor Cells Undergo infusion of genetically modified hematopoietic progenitor cell therapy
Other Name: Genetically Engineered HSPCs Other: Laboratory Biomarker Analysis Correlative studies Procedure: Leukapheresis Undergo leukapheresis
Other Names:
Drug: Methylprednisolone Given IV
Other Names:
Drug: Plerixafor Given SC
Other Names:
Drug: Prednisone Given PO
Other Names:
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- Toxicity of gene transfer [ Time Frame: Up to 15 years ]Adverse events will be graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.
- Hematological and non-hematological organ toxicity [ Time Frame: Up to 15 years ]Adverse events will be graded by CTCAE, version 4.
- Development of insertional mutagenesis or hematologic malignancy [ Time Frame: Up to 15 years ]Adverse events will be graded by CTCAE, version 4.
- Development of replication competent lentivirus [ Time Frame: Up to 15 years ]Adverse events will be graded by CTCAE, version 4.
- Efficacy of G-CSF and plerixafor mobilization in Fanconi anemia (FA) patients [ Time Frame: Up to 6 days ]
- Efficacy of lineage depletion of bone marrow or mobilized cell product [ Time Frame: Up to 15 years ]
- Transduction efficiency [ Time Frame: Day 0 ]After completion of lentiviral transduction, the percent gene modified cells will be determined by molecular studies.
- Detectable levels of transduced cells in blood and marrow [ Time Frame: Up to 1 year ]Blood and bone marrow samples will be assayed by real-time quantitative polymerase chain reaction.
- Improved blood counts [ Time Frame: Up to 15 years ]Complete blood counts will be monitored, initially weekly, then monthly during the first year, then quarterly during the 2nd year after infusion.
- Demonstrable functional expression by growth of recipient cells in mitomycin C [ Time Frame: 3 months ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 4 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01331018
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Hans-Peter Kiem | Fred Hutch/University of Washington Cancer Consortium |
| Responsible Party: | Fred Hutchinson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01331018 |
| Other Study ID Numbers: |
2097.00 NCI-2011-00202 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) RG9212015 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
| First Posted: | April 7, 2011 Key Record Dates |
| Last Update Posted: | July 11, 2023 |
| Last Verified: | July 2023 |
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Fanconi Syndrome Anemia Fanconi Anemia Hematologic Diseases Anemia, Hypoplastic, Congenital Anemia, Aplastic Congenital Bone Marrow Failure Syndromes Bone Marrow Failure Disorders Bone Marrow Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Renal Tubular Transport, Inborn Errors Kidney Diseases Urologic Diseases |
Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Plerixafor Prednisone Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Cortisone Prednisolone hemisuccinate Prednisolone phosphate Lenograstim |