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Gene Therapy for Fanconi Anemia, Complementation Group A

Primary Purpose

Fanconi Anemia Complementation Group A

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RP-L102
Sponsored by
Rocket Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia Complementation Group A focused on measuring anemia, bone marrow failure, gene therapy

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent
  2. Patients of the complementation group FA-A
  3. Minimum age: 1 year and a minimum weight of 8 kg
  4. At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion)
  5. If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB) parameters should meet two of the three following criteria:

    • Hemoglobin: ≥11g/dL
    • Neutrophils: ≥900 cells/μL
    • Platelets: ≥60,000 cells/μL
  6. Provide informed consent in accordance with current legislation
  7. Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial

Exclusion Criteria:

  1. Subjects with an available and medically eligible HLA-identical sibling donor.
  2. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those reported as variant(s) of normal in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial.
  3. Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease (≥1 NCI CTCAE grade) in at least one blood lineage over time must be documented to enable eligibility, as should <5% resistance of bone marrow colony forming cells (CFCs) to 10nM MMC; whenever possible potential mosaicism should also be evaluated by gene sequencing of MMC-resistant CFCs).
  4. Lansky performance status ≤60%.
  5. Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
  6. Pre-existing sensory or motor impairment ≥grade 2 according to the criteria of the NCI.
  7. Pregnant or breastfeeding women.
  8. Hepatic dysfunction as defined by either:

    • Bilirubin >3.0 × the upper limit of normal (ULN) or
    • Alanine aminotransferase (ALT) > 5.0 × ULN or
    • Aspartate aminotransferase (AST) > 5.0 × ULN

    For subjects with bilirubin, ALT or AST above ULN, a workup to identify the etiology of liver abnormality should be conducted prior to confirmation of eligibility as stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron overload, drug injury or other causes.

  9. Renal dysfunction requiring either hemodialysis or peritoneal dialysis.
  10. Pulmonary dysfunction as defined by either:

    • Need for supplemental oxygen during the prior 2 weeks in absence of acute infection or
    • Oxygen saturation by pulse oximetry <90%.
  11. Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years.
  12. Subject is receiving androgens (i.e. danazol, oxymetholone).
  13. Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure.

Sites / Locations

  • Stanford UniversityRecruiting
  • University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RP-L102

Arm Description

RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene

Outcomes

Primary Outcome Measures

Phenotypic correction of bone marrow colony forming units after infusion of RP-L102
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).

Secondary Outcome Measures

Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Assessment of the percentage of peripheral blood T-cells with diepoxybutane (DEB)-induced chromosomal aberrations
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
The level of gene marking of the FANCA-lentiviral vector (LV) provirus in total peripheral blood cells is at least 0.1 vector copy number (VCN) in peripheral blood cells during months 12-36 post-infusion
Prevention or rescue of bone marrow failure after infusion of RP-L102
Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion.

Full Information

First Posted
January 24, 2020
Last Updated
November 23, 2020
Sponsor
Rocket Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04248439
Brief Title
Gene Therapy for Fanconi Anemia, Complementation Group A
Official Title
A Phase 2 Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 15, 2020 (Actual)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rocket Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this study is to assess the therapeutic efficacy of a hematopoietic cell-based gene therapy for patients with Fanconi anemia, subtype A (FA-A). Hematopoietic stem cells from mobilized peripheral blood of patients with FA-A will be transduced ex vivo (outside the body) with a lentiviral vector carrying the FANCA gene. After transduction, the corrected stem cells will be infused intravenously back to the patient with the goal of preventing bone marrow failure.
Detailed Description
This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia Complementation Group A
Keywords
anemia, bone marrow failure, gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RP-L102
Arm Type
Experimental
Arm Description
RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene
Intervention Type
Biological
Intervention Name(s)
RP-L102
Intervention Description
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene
Primary Outcome Measure Information:
Title
Phenotypic correction of bone marrow colony forming units after infusion of RP-L102
Description
During months 12-36 post-infusion, the survival of bone marrow colony forming units to 10nM mitomycin C (MMC) increases to over or equal to 10% with respect to values determined at baseline (pretreatment evaluation).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Description
Assessment of the percentage of peripheral blood T-cells with diepoxybutane (DEB)-induced chromosomal aberrations
Time Frame
3 years
Title
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
Description
The level of gene marking of the FANCA-lentiviral vector (LV) provirus in total peripheral blood cells is at least 0.1 vector copy number (VCN) in peripheral blood cells during months 12-36 post-infusion
Time Frame
3 years
Title
Prevention or rescue of bone marrow failure after infusion of RP-L102
Description
Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fanconi anemia as diagnosed by chromosomal fragility assay of cultured lymphocytes in the presence of DEB or a similar DNA-crosslinking agent Patients of the complementation group FA-A Minimum age: 1 year and a minimum weight of 8 kg At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection OR (see subsequent criterion) If the number of CD34+ cells/ μL in BM is in the range of 10-29, peripheral blood (PB) parameters should meet two of the three following criteria: Hemoglobin: ≥11g/dL Neutrophils: ≥900 cells/μL Platelets: ≥60,000 cells/μL Provide informed consent in accordance with current legislation Women of childbearing age must have a negative urine pregnancy test at the baseline visit, and accept the use of an effective contraception method during participation in the trial Exclusion Criteria: Subjects with an available and medically eligible HLA-identical sibling donor. Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities other than those reported as variant(s) of normal in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial. Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease (≥1 NCI CTCAE grade) in at least one blood lineage over time must be documented to enable eligibility, as should <5% resistance of bone marrow colony forming cells (CFCs) to 10nM MMC; whenever possible potential mosaicism should also be evaluated by gene sequencing of MMC-resistant CFCs). Lansky performance status ≤60%. Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study. Pre-existing sensory or motor impairment ≥grade 2 according to the criteria of the NCI. Pregnant or breastfeeding women. Hepatic dysfunction as defined by either: Bilirubin >3.0 × the upper limit of normal (ULN) or Alanine aminotransferase (ALT) > 5.0 × ULN or Aspartate aminotransferase (AST) > 5.0 × ULN For subjects with bilirubin, ALT or AST above ULN, a workup to identify the etiology of liver abnormality should be conducted prior to confirmation of eligibility as stipulated in exclusion criterion 5, including evaluation of viral hepatitis, iron overload, drug injury or other causes. Renal dysfunction requiring either hemodialysis or peritoneal dialysis. Pulmonary dysfunction as defined by either: Need for supplemental oxygen during the prior 2 weeks in absence of acute infection or Oxygen saturation by pulse oximetry <90%. Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years. Subject is receiving androgens (i.e. danazol, oxymetholone). Subject is receiving other investigational therapy for treatment/prevention of FA-associated bone marrow failure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Information
Phone
646-627-0033
Email
FAclinicaltrial@rocketpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Agnieszka Czechowicz, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Margaret MacMillan, MD, MSc
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabeth Merkel
Email
scgt_clinical_trials_office@lists.stanford.edu
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

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Gene Therapy for Fanconi Anemia, Complementation Group A

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