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Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study


Phase 2
N/A
N/A
Open (Enrolling)
Both
Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Childhood Acute Myeloid Leukemia in Remission, Childhood Myelodysplastic Syndromes, de Novo Myelodysplastic Syndromes, Fanconi Anemia, Previously Treated Myelodysplastic Syndromes

Thank you

Trial Information

Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study


PRIMARY OBJECTIVES:

I. Identify doses of TBI that lead to sufficient probability of donor engraftment (> 5%
donor cluster of differentiation [CD]3 chimerism) by day +200.

II. Evaluate the probability of severe acute graft-versus-host disease (GVHD).

SECONDARY OBJECTIVES:

I. Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and
recurrent hematopoietic malignancy in those patients with a prior underlying history of
such.

II. Examine the degree to which mixed chimerism provides for amelioration of symptoms (i.e.,
infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone
marrow failure.

III. Determine if the FA complementation group and % initial mosaicism predict engraftment
and RRT outcomes.

OUTLINE: Patients are assigned to 1 of 4 treatment arms.

NOTE: Patients no longer receive pre-transplant cyclophosphamide as of February 2009.

After completion of study treatment, patients are followed up at 6 months and then annually
thereafter.


Inclusion Criteria:



- Any patient with FA and bone marrow (BM) failure involving 2 of the following 3
lineages: granulocyte count < 0.5 x 10^9/L, platelet count < 20 x 10^9/L, or
hemoglobin < 8 g/dL

- Any patient with FA who requires red blood cell or platelet transfusions because of
marrow failure

- Any patient with FA who has a life-threatening BM failure involving a single
hematopoietic lineage

- Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic
malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in
morphological remission (defined as absence of circulating blasts and bone marrow
blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not
required for remission status

- Patients must have a negative cytotoxic cross match with donor

- DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical
for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1
loci of the unshared haplotype

- DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by
Deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at
the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR
a single DQB1 mismatch is allowed

- DONOR: Bone marrow will be the only allowed hematopoietic stem cell source

- DONOR: Haploidentical donor selection will be based on standard institutional
criteria, otherwise no specific prioritization will be made amongst the suitable
available donors

Exclusion Criteria:

- Patients having available HLA-matched related donors

- Significant organ dysfunction that would prevent compliance with conditioning, GVHD
prophylaxis, or would severely limit the probability of survival, such as liver
disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis
confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or
cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction,
shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required
with principal investigator [PI] having final approval of eligibility)

- Human immunodeficiency virus (HIV) seropositive patients

- Fertile females who are unwilling to use contraceptive techniques during and for the
twelve months following treatment, as well as females who are pregnant or actively
breast feeding

- Fertile males who are unwilling to use contraceptive techniques during and for the
twelve months following treatment

- AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow
blasts >= 5% as assessed by morphology

- Active infectious disease concerns

- Karnofsky performance score < 50 or Lansky performance score < 40

- DONOR: Donors found to have Fanconi Anemia based on chromosomal breakage analysis

- DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1
x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to
be bone marrow donors

- DONOR: HIV-positive donors

- DONOR: Donors who are cross-match positive with recipient

- DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at
HLA-A, B, or C and the donor is mismatched at that locus, the donor should be
avoided; exceptions must be discussed with the primary investigator (PI)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Doses of TBI associated with acceptable levels of engraftment

Outcome Time Frame:

By day 200

Safety Issue:

No

Principal Investigator

Hans-Peter Kiem

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

2064.00

NCT ID:

NCT00453388

Start Date:

February 2007

Completion Date:

Related Keywords:

  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Myelodysplastic Syndromes
  • de Novo Myelodysplastic Syndromes
  • Fanconi Anemia
  • Previously Treated Myelodysplastic Syndromes
  • Congenital Abnormalities
  • Anemia
  • Fanconi Anemia
  • Fanconi Syndrome
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Cleveland Clinic FoundationCleveland, Ohio  44195
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Vanderbilt UniversityNashville, Tennessee  37232-6305
Children's Hospital of WisconsinMilwaukee, Wisconsin  53201