HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

Part of paid clinical trials in New York, New York.

Sponsor
Children's Hospital Medical Center, Cincinnati
Study ID
NCT02143830
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Acute Myelogenous Leukemia (AML)
  • Fanconi Anemia
  • Myelodysplastic Syndrome (MDS)
  • Severe Marrow Failure

Eligibility Criteria

Sex
ALL
Age
3 Months - N/A
Healthy Volunteers
Not accepted

Interventions

  • Busulfan — DRUG
    A standard dose of busulfan, associated with excellent outcomes in our previous trial will be used for young patients with marrow aplasia (arm A). A higher dose of busulfan will be used in younger patients with MDS and AML (arm B) to maximize disease control. A lower dose of busulfan will be used in older patients (arm C) to minimize toxicity.
  • Cyclophosphamide — DRUG
    Arms A, B and C - Cytoxan will be given as a 1-2 hour infusion for 4 days. The dose will be adjusted according to patients ideal body weight for obese patients.
  • Fludarabine — DRUG
    Arms A, B and C - Fludarabine will be given IV over 30 minutes daily for 4 days. The dose will be adjusted according to renal function according to Institutional guidelines.
  • rabbit ATG — DRUG
    Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.
  • G-CSF — DRUG
    All patients will also receive G-CSF post-transplant to foster engraftment.
  • Peripheral blood stem cell — BIOLOGICAL
    The source of stem cells for all patients will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 4-6 days. T-cell depletion will be uniformly performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device).

Study Details

The purpose of this study is to determine whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Patients will undergo a transplant utilizing mis-matched related or matched unrelated donors following a preparative regimen of busulfan, fludarabine, anti-thymocyte globulin and cyclophosphamide.

Key Dates

Start date
Apr 30, 2014
Status verified
Nov 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2028

Study Design

Enrollment
70 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A: Good Risk Patients
    Patients 18 years old or younger with marrow aplasia or single lineage cytopenias will be receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days), as used in our most current study that led to \> 90% survival rates . Busulfan pharmacokinetics will not be used. All patients will receive rabbit ATG (4 doses x 4 days) prior to and granulocyte-colony stimulating factor (G-CSF) after transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells for all patients will be peripheral blood stem cells mobilized by treatment of the donor with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). Enrollment on this arm will include up to 50 patients.
  • Experimental: Arm B: Intermediate Risk Patients
    Patients 18 years old or younger with MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). Busulfan pharmacokinetics will be used in this arm, as the dose of busulfan is higher. All patients will receive rabbit ATG (thymoglobulin) (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for prophylaxis against GVHD. The source of the stem cells for all patients will be peripheral blood stem cells induced and mobilized by treatment of the donor. T-cell will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled in this arm will be 10.
  • Experimental: Arm C: High Risk Patients
    Patients 19 years old or older with marrow aplasia or MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). In this study, we will test whether outcomes can be improved, yet engraftment maintained, with a slightly reduced dose of busulfan. Patients will receive rabbit ATG (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells will be peripheral blood stem cells collected from donors treated with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled will be 10.

Primary Outcome Measure

Graft Failure or Rejection [ Time Frame: 5 years ]

Central Contacts

Locations (3)

FacilityCityStateZIPSite coordinators
Memorial Sloan Kettering Cancer CenterNew YorkNew York10174-
Cincinnati Children's Hospital Medical CenterCincinnatiOhio45229
Parinda Mehta, MD (PRINCIPAL_INVESTIGATOR)
Fred Hutchinson Cancer Research CenterSeattleWashington98109
Sheri Ballard
[email protected]
206-667-4222
K. Scott Baker, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in New York, NY

By research site
Memorial Sloan Kettering Cancer Center· New York, NYCincinnati Children's Hospital Medical Center· Cincinnati, OHFred Hutchinson Cancer Research Center· Seattle, WA

Related Studies