A Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
Overview
- Phase
- Phase 2
- Intervention
- Busulfan
- Conditions
- Fanconi Anemia
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 3
- Locations
- 3
- Primary Endpoint
- Graft Failure or Rejection
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
The goal of this study is to see if the study therapy can decrease the chemotherapy-related side effects while maximizing the effectiveness of disease control. The physicians will also be studying the effect of removing T-cells from the donor"s stem cells before transplant. T-cells are a type of white blood cell that may help cause a serious side effect of transplant called Graft versus Host Disease (GVHD). The way it removes the T-cells from the donor stem cells is actually by selecting only the stem cells (called CD34 cells) by using a device called CliniMACS. This process is called CD34 selection. The CliniMACS® device is currently under the supervision of the FDA .
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane \[DEB\] chromosomal breakage testing at a CLIA approved laboratory).
- •Patients must have one of the following hematologic diagnoses:
- •Severe Aplastic Anemia (SAA), with bone marrow cellularity of \<25% OR Severe Isolated Single lineage Cytopenia
- •AND at least one of the following features:
- •Platelet count \<20 x 10\^9/L or platelet transfusion dependence\*
- •ANC \<1000 x 10\^9/L
- •Hgb \<8 gm/dl or red cell transfusion dependence\*
- •Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification)
- •MDS at any stage, based on either one of the following classifications:
- •WHO Classification
Exclusion Criteria
- •Active CNS leukemia Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
- •Active uncontrolled viral, bacterial or fungal infection Patient seropositive for HIV-I/II; HTLV -I/II
Arms & Interventions
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Busulfan
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Fludarabine
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Cyclophosphamide
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Anti-Thymocyte Globulin (Rabbit)
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: The CliniMACS device
Good Risk Patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: G-CSF
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Busulfan
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Fludarabine
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Cyclophosphamide
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Anti-Thymocyte Globulin (Rabbit)
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: The CliniMACS device
Intermediate risk patients
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: G-CSF
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Anti-Thymocyte Globulin (Rabbit)
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Busulfan
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Fludarabine
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: Cyclophosphamide
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: The CliniMACS device
High risk patients
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Intervention: G-CSF
Outcomes
Primary Outcomes
Graft Failure or Rejection
Time Frame: 5 years
Primary non-engraftment is diagnosed when the patient fails to achieve an ANC ≥500/µl at any time in the first 28 days post-transplant. If (1) after achievement of an ANC ≥500/mm\^3, the ANC declines to \<500/mm\^3 for more than 3 consecutive days in the absence of relapse, or, (2) there is absence of donor cells in the marrow and/or blood as demonstrated by chimerism assay in the absence of relapse, a diagnosis of secondary graft failure is made. The patient is not evaluable for graft failure or rejection if recurrence of host MDS is detected concurrently.