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Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation


Phase 2
N/A
69 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma, Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myeloproliferative Neoplasms

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Trial Information

Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation


OBJECTIVES:

- Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell
transplantation by demonstrating that the risk of treatment-related mortality during
the first 6 months is an acceptable rate of less than 40% in patients with relapsed
hematologic malignancies after prior high-dose chemotherapy and autologous stem cell
transplantation.

- Determine the response rates (disease-specific partial and complete response) in
patients treated with this regimen.

- Determine the 6-month and 12-month probabilities of response in patients treated with
this regimen.

- Determine the distribution of time-to-progression in patients responding to this
regimen.

- Determine the percent donor chimerism in patients treated with this regimen.

- Determine the risk of acute and chronic graft-vs-host disease in patients treated with
this regimen.

- Determine the toxic effects of this regimen in these patients.

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

OUTLINE: This is an open-label study.

- Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3
and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.

- Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor
receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily
on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3,
and 6. Patients with a matched related or matched unrelated donor receive oral (or IV
if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180
followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral
mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit
anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than
50% at day 60 or patient has progressive disease

- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or
peripheral blood stem cell transplantation on days 0 and 1. Patients then receive
filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood
counts recover.

- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an
HLA-identical donor), patients with stable or progressive disease and no active GVHD
may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months
for 3 years.

PROJECTED ACCRUAL: A total of 20-80 patients will be accrued for this study within 10-40
months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed hematologic malignancy, including one of the following:

- Chronic lymphocytic leukemia (CLL)

- Absolute lymphocytosis greater than 5,000/mm^3

- Lymphocytes must appear morphologically mature with less than 55%
prolymphocytes

- Lymphocyte phenotype with expression of CD19 and CD5

- Prolymphocytic leukemia (PLL)

- Morphologically confirmed

- Absolute lymphocytosis greater than 5,000/mm^3

- More than 55% prolymphocytes

- Non-Hodgkin's lymphoma or Hodgkin's lymphoma

- Any WHO histologic subtype allowed except mantle cell lymphoma

- Core biopsies allowed if they contain adequate tissue for primary diagnosis
and immunophenotyping

- No bone marrow biopsy as the sole diagnostic means for follicular lymphoma

- Multiple myeloma

- Active disease requiring treatment

- Durie-Salmon stage I, II, or III

- Acute myeloid leukemia

- Documented control (i.e., less than 10% bone marrow blasts and no
circulating blasts)

- Myelodysplastic syndromes

- Documented disease by WHO criteria

- Must have evidence of relapse/progression at least 6 months after prior high-dose
chemotherapy with autologous hematopoietic stem cell support

- Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic
evidence of mantle cell lymphoma

- Availability of any of the following donor types:

- HLA-identical sibling (6/6)

- 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C,
DRB1, and DQB1 loci

- Only a single mismatch at one class I or II allele allowed

- 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B,
C, DRB1, and DQB1 loci

- No syngeneic donors

PATIENT CHARACTERISTICS:

Age

- Under 70

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- Bilirubin no greater than 3 times upper limit of normal (ULN)

- AST no greater than 3 times ULN

Renal

- Creatinine clearance at least 40 mL/min

Cardiovascular

- LVEF at least 30% by MUGA

Pulmonary

- DLCO greater than 40%

- No symptomatic pulmonary disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No uncontrolled diabetes mellitus

- No active serious infection

- No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy

Surgery

- More than 4 weeks since prior surgery

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related mortality

Outcome Time Frame:

6 months post transplant

Safety Issue:

Yes

Principal Investigator

Asad Bashey, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Diego

Authority:

United States: Federal Government

Study ID:

CDR0000269301

NCT ID:

NCT00053196

Start Date:

December 2002

Completion Date:

August 2010

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasms
  • refractory chronic lymphocytic leukemia
  • prolymphocytic leukemia
  • recurrent adult Hodgkin lymphoma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • previously treated myelodysplastic syndromes
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • secondary myelodysplastic syndromes
  • de novo myelodysplastic syndromes
  • recurrent adult acute myeloid leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • atypical chronic myeloid leukemia, BCR-ABL negative
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • 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)
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State UniversityColumbus, Ohio  43210-1240
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Massey Cancer Center at Virginia Commonwealth UniversityRichmond, Virginia  23298-0037
Cancer Institute of New Jersey at the Cooper University Hospital - VoorheesCamden, New Jersey  08103
Beebe Medical CenterLewes, Delaware  19958
St. Francis HospitalWilmington, Delaware  19805
Union Hospital Cancer Center at Union HospitalElkton MD, Maryland  21921
Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224-1791