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Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells


Phase 1
18 Years
55 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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Trial Information

Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells


OBJECTIVES:

- Determine the feasibility and efficacy of a reduced-intensity conditioning regimen
comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic
peripheral blood stem cell transplantation (PBSCT) in patients with hematologic
malignancies.

- Determine the toxicity of this regimen in these patients.

- Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells,
administered after allogeneic PBSCT, in these patients.

OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted
donor T cells.

- T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood
mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are
irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order
to selectively deplete T cells from the donor PBMCs.

- Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5,
fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day
-4, and thiotepa IV on days -3 to -2.

- Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1.

- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo
allogeneic PBSC transplantation on day 0.

- LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2
immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on
approximately day 28.

Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated,
selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the dose preceding that at which 2 of 6 patients experience
dose-limiting-toxicity.

After completion of study treatment, patients are followed weekly for 100 days
post-transplantation and then periodically for survival.

PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following hematologic malignancies:

- Chronic myelogenous leukemia

- Accelerated phase or blast phase

- Acute myeloid leukemia, meeting any of the following criteria:

- In second or subsequent remission

- In primary induction failure

- In partial remission

- In resistant relapse

- Chronic lymphocytic leukemia

- In Richter's transformation

- High-grade non-Hodgkin's lymphoma

- Refractory to standard treatment

- Myeloproliferative disorders

- Undergoing transformation to terminal stages

- Myelodysplastic syndromes (MDS), including any of the following:

- Refractory anemia with excess blasts

- Transformation to acute leukemia

- MDS secondary to chemotherapy

- Partially-matched related family donor available

- One HLA haplotype match

- No HLA-matched (10/10 or 9/10) sibling donor or unrelated donor available NOTE: A new
classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The
terminology of "indolent" or "aggressive" lymphoma will replace the former
terminology of "low", "intermediate", or "high" grade lymphoma. However, this
protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

- 18 to 55

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- SGOT and SGPT < 3 times upper limit of normal (ULN)

- No active or persistent viral hepatitis

Renal

- Creatinine < 2.0 mg/dL* OR

- Creatinine clearance > 60 mL/min* NOTE: *Unless due to malignancy

Cardiovascular

- LVEF ≥ 45%

Pulmonary

- DLCO ≥ 60% of predicted* (corrected for hemoglobin) NOTE: *Unless patient is given
clearance by a pulmonary consultation

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for up to 2 years after
completion of study treatment

- HIV negative

- Human T cell lymphotrophic virus type 1 negative

- No serious co-morbid medical condition

- No other medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Not specified

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Erkut Bahceci, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Yale University

Authority:

United States: Federal Government

Study ID:

CDR0000413698

NCT ID:

NCT00104975

Start Date:

February 2005

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • accelerated phase chronic myelogenous leukemia
  • recurrent adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • secondary myelodysplastic syndromes
  • chronic myelomonocytic leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic eosinophilic leukemia
  • primary myelofibrosis
  • chronic neutrophilic leukemia
  • essential thrombocythemia
  • polycythemia vera
  • adult acute myeloid leukemia in remission
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • 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)
  • recurrent adult acute myeloid leukemia
  • refractory chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • stage III adult Burkitt lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • atypical chronic myeloid leukemia, BCR-ABL1 negative
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Yale Cancer CenterNew Haven, Connecticut  06520-8028