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A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-Compatible Related or Unrelated Donors in Patients With B Cell Lymphoid Malignancies


Phase 2
18 Years
70 Years
Open (Enrolling)
Both
Leukemia, Lymphoma

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Trial Information

A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-Compatible Related or Unrelated Donors in Patients With B Cell Lymphoid Malignancies


OBJECTIVES:

Primary

- Determine the overall and event-free survival at 1 year in patients with B-cell
non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with a nonmyeloablative
conditioning regimen, rituximab, and allogeneic hematopoietic stem cell
transplantation.

Secondary

- Determine the speed of neutrophil and platelet recovery in patients treated with this
regimen.

- Determine the incidence and speed of donor-derived engraftment in these patients.

- Determine the incidence and severity of acute graft versus host disease (GVHD) at 100
days in patients treated with this regimen.

- Determine the incidence and severity of chronic GVHD at 1 year in patients treated with
this regimen.

- Correlate the incidence of serious infectious complications with immune recovery in
patients treated with this regimen.

- Determine the response in patients treated with this regimen.

- Determine the incidence of transplant-related mortality at 100 and 180 days in these
patients.

- Determine the incidence of malignant relapse or disease progression at 1 and 2 years in
these patients.

- Determine the probabilities of overall and event-free survival at 2 years in patients
treated with this regimen.

OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched
unrelated or single HLA allele-disparate related or unrelated).

- Rituximab therapy: Patients receive rituximab IV on day -8 or -7 and on days 21, 28,
35, and 42.

- Nonmyeloablative conditioning: Patients receive fludarabine phosphate IV over 30
minutes on days -6 to -2, cyclophosphamide IV on day -6, and anti-thymocyte globulin
(ATG)* IV over 4-6 hours on days -3 and/or -2. Patients undergo total-body irradiation
on day -1.

NOTE: *Patients with HLA-matched sibling donors do not receive ATG.

- Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo filgrastim
(G-CSF)-mobilized allogeneic HSCT on day 0. Patients receive filgrastim (G-CSF) IV or
subcutaneously beginning on day 7 and continuing until blood counts recover.

- Graft versus host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours
or orally twice daily on days -3 to 100 followed by a taper and mycophenolate mofetil
IV or orally twice daily on days -3 to 45 followed by a taper, in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for 2 years and
then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of
the following subtypes:

- Diffuse large cell lymphoma*, meeting 1 of the following criteria:

- Relapsed disease after initial therapy, but failed to mobilize or had
bone marrow involvement and therefore is not suitable for an
autologous stem cell transplantation

- High-intermediate- or high-risk second-line, age-adjusted
International Prognostic Index score and in second complete remission
(CR) or partial remission (PR) after autologous stem cell
transplantation

- Failed prior autologous stem cell transplantation and in PR or better
after salvage chemotherapy

- Large cell transformation of indolent NHL or chronic lymphocytic leukemia
(CLL), meeting the following criteria:

- In CR or PR of the large cell component of disease after salvage
chemotherapy or autologous stem cell transplantation

- Mantle cell lymphoma*, meeting 1 of the following criteria:

- High-risk disease (e.g., p53 positivity) and in first CR or PR after
initial therapy

- Relapsed disease after initial therapy and in second or third CR or PR
after salvage chemotherapy NOTE: *No progressive disease at allograft
work-up

- CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or
marginal zone NHL) OR CLL

- Second or subsequent progression (pre-allograft cytoreduction necessary,
but CR or PR not required)

- Relapsed disease must be biopsy-proven

- Must have received pre-allograft salvage chemotherapy, including 1 of the following:

- Single autologous stem cell transplantation using high-dose chemotherapy
conditioning within the past 120 days

- At least 2 courses of intensive combination chemotherapy (e.g., RICE [rituximab,
ifosfamide, carboplatin, etoposide]), according to diagnosis, within the past 80
days

- CLL patients who have received CAMPATH do not have to receive pre-allograft
salvage chemotherapy

- HLA-compatible related or unrelated donor available

- HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high
resolution typing

- One allele mismatch allowed

PATIENT CHARACTERISTICS:

- Karnofsky performance status 70-100%

- Creatinine < 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min

- Bilirubin < 2.5 mg/dL

- AST and ALT ≤ 3 times upper limit of normal (unless benign congenital
hyperbilirubinemia is present)

- Spirometry and corrected DLCO ≥ 50% of normal

- LVEF ≥ 40%

- Albumin ≥ 2.5 g/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active uncontrolled infection, including active infection with Aspergillus or
other mold

- No HIV infection

- No hepatitis B antibody or antigen positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic transplantation

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall and event-free survival at 1 year

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Hugo R. Castro-Malaspina, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

06-150

NCT ID:

NCT00425802

Start Date:

November 2006

Completion Date:

November 2014

Related Keywords:

  • Leukemia
  • Lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • B-cell chronic lymphocytic leukemia
  • refractory chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • noncontiguous stage II mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • recurrent marginal zone lymphoma
  • splenic marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021