Pilot Study Of T-Cell-Depleted Peripheral Blood Stem Cell Transplantation From Partially Matched Related Donors For Patients With High-Risk Leukemia


Phase 2
10 Years
50 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic/Myeloproliferative Diseases

Thank you

Trial Information

Pilot Study Of T-Cell-Depleted Peripheral Blood Stem Cell Transplantation From Partially Matched Related Donors For Patients With High-Risk Leukemia


OBJECTIVES:

- Determine the safety of a preparative regimen comprising total body irradiation,
cyclophosphamide, thiotepa, and fludarabine, but without anti-thymocyte globulin, in
patients with high-risk leukemia treated with peripheral blood stem cell
transplantation from partially matched related donors.

- Determine the incidence of graft failure, acute graft-versus-host disease (GVHD), and
treatment-related mortality in patients treated with this regimen.

- Determine rates of chronic GVHD and relapse in patients treated with this regimen.

- Determine disease-free and overall survival in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive a preparative regimen comprising total lymphoid irradiation once daily on
days -13 to -11; cyclophosphamide IV over 1 hour on days -8 and -7; thiotepa IV over 4 hours
every 12 hours on day -6; fludarabine IV over 30 minutes on days -5 to -1; and total body
irradiation once on day -1. Patients also receive cyclosporine IV over 12 hours on days -8
to -1 and methylprednisolone IV twice daily on days -3 and -2. Patients receive
CD34-enriched T-cell-depleted allogeneic stem cell infusion on day 0.

Patients with disease progression or uncontrolled infection but without grade II or greater
graft-versus-host disease may receive up to 3 donor lymphocyte infusions at least 4 weeks
apart until disease regression.

Patients are followed at least weekly until day 100 and then at 6, 12, 18, 24, 36, and 48
months.

PROJECTED ACCRUAL: A total of 20-51 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- High-risk myelodysplastic syndromes (MDS), meeting 1 of the following criteria:

- Transformation to acute leukemia defined by at least 15% blasts

- Secondary to prior treatment with chemotherapy and/or radiotherapy

- Presence of complex cytogenetics (at least 3 karyotypic abnormalities)

- Monosomy or deletion of chromosome 7

- Acute myeloid leukemia (AML), meeting 1 of the following criteria :

- High-risk AML in first remission and meeting 1 of the following criteria:

- At least 3 karyotypic abnormalities

- Monosomy or deletion of chromosome 5 or 7 = 11q23 chromosomal
abnormality

- Prior diagnosis of MDS

- Received prior radiotherapy or chemotherapy

- In second or subsequent remission

- Primary induction failure or partial remission

- Untested or sensitive relapse

- Chronic myelogenous leukemia, meeting 1 of the following criteria:

- Blast crisis

- Accelerated phase disease that has failed prior treatment with imatinib
mesylate, defined as a failure to achieve hematologic response after 3
months of standard dose (600 mg/day) therapy or disease progression on
therapy

- Myeloproliferative disease

- The following diagnoses are eligible:

- Agnogenic myeloid metaplasia

- Essential thrombocythemia

- Polycythemia vera

- Must have evidence of transformation to acute leukemia

- Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:

- High-risk ALL in first remission defined by 1 of the following:

- t(9;22) or 11q23 chromosomal abnormality

- Complete response at least 4 weeks after induction therapy OR
requiring at least 2 induction regimens

- Second or subsequent remission

- No relapsed leukemia refractory to appropriate salvage therapy

- Availability of an HLA-mismatched family donor

- Donor age 75 or under

- No better donor alternative (i.e., HLA-matched related or unrelated stem cell donor)
is available

PATIENT CHARACTERISTICS:

Age

- 10 to 50

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months

Hematopoietic

- See Disease Characteristics

Hepatic

- Bilirubin no greater than 4 mg/dL

- Transaminases no greater than 3 times upper limit of normal

Renal

- Creatinine no greater than 2.0 mg/dL OR

- Creatinine clearance at least 60 mL/min

Cardiovascular

- LVEF at least 40%

Pulmonary

- DLCO at least 65% of predicted

Other

- Not pregnant

- Negative pregnancy test

- HIV negative

- No other prior malignancy except basal cell or squamous cell skin cancer or a remote
history of cancer now considered cured

- No major organ dysfunction that would preclude transplantation

- No major anticipated illness or organ failure that would preclude transplantation

- No severe psychiatric illness or mental deficiency that would preclude giving
informed consent or complying with study

- No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of graft failure 100 days post-transplant

Principal Investigator

Bipin N. Savani, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)

Authority:

Unspecified

Study ID:

CDR0000315900

NCT ID:

NCT00066417

Start Date:

Completion Date:

January 2007

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Myelodysplastic/Myeloproliferative Diseases
  • essential thrombocythemia
  • polycythemia vera
  • blastic phase chronic myelogenous leukemia
  • secondary myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • adult acute myeloid leukemia in remission
  • childhood acute myeloid leukemia in remission
  • de novo myelodysplastic syndromes
  • secondary acute myeloid leukemia
  • accelerated phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • recurrent adult acute myeloid leukemia
  • relapsing chronic myelogenous leukemia
  • recurrent childhood acute myeloid leukemia
  • chronic idiopathic myelofibrosis
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • Leukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location
NIH - Warren Grant Magnuson Clinical Center Bethesda, Maryland  20892-1182