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A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilical Cord Blood 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 Unrelated Donor Umbilical Cord Blood in Patients With B Cell Lymphoid Malignancies


OBJECTIVES:

Primary

- Determine the overall and event-free survival at 1 year in patients with B-cell
lymphoid malignancies treated with a nonmyeloablative conditioning regimen, rituximab,
and umbilical cord blood (UCB) transplantation (UCBT).

Secondary

- Determine the speed of neutrophil and platelet recovery post allograft in these
patients.

- Determine the incidence and speed of donor-derived engraftment and contribution of each
UCB unit to engraftment in these patients.

- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days
in these patients.

- Determine the incidence and severity of chronic GVHD at 1 year in these patients.

- Determine the incidence of serious infectious complications and correlate with
laboratory measurements of immune recovery in these patients.

- Determine the response to vaccination after UCBT in these patients.

- Determine the incidence of treatment-related mortality at 100 days 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 after UCBT in
these patients.

- Determine the performance of laboratory studies investigating double-unit biology and
correlate with unit engraftment in these patients.

OUTLINE:

- Pre-transplant rituximab therapy: Patients receive rituximab IV on days -8 or -7 and on
day -4.

- Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over
30 minutes on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo
total-body irradiation on day -1.

- Umbilical cord blood transplantation: Patients undergo umbilical cord blood
transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously
beginning on day 7 and continuing until blood counts recover.

- Post-transplant rituximab therapy: Patients receive rituximab IV on days 7, 14, 21, and
28.

- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or
orally twice daily on days -3 to 100, followed by a taper. Patients also receive
mycophenolate mofetil IV or orally three times daily on days -3 to 45, followed by a
taper.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- CD20+* aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the
following:

- Diffuse large cell (DLC) NHL 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 (IPI) score and in second complete
remission (CR) or partial remission (PR) after prior autologous stem
cell transplantation

- Failed prior autologous stem cell transplantation and in at least PR
after salvage chemotherapy

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

- CR/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, as defined by p53 positivity and in first CR/PR after
initial therapy

- Relapsed disease after initial therapy and in second or third CR/PR
after salvage chemotherapy

- CD20+* indolent NHL or CLL meeting the following criteria:

- Must be in second or subsequent progression (pre-allograft cytoreduction
necessary but CR/PR not required)

- Indolent NHL includes, but is not limited to, any of the following:

- Follicular NHL

- Small cell NHL

- Marginal zone NHL NOTE: *CD20 positivity must be demonstrated within
the past 12 months

- Relapsed disease must be biopsy proven

- Prior pre-allograft cytoreduction may have included 1 of the following:

- Single autologous stem cell transplantation with high-dose chemotherapy
conditioning, if appropriate, and no conditioning prior to transplantation

- Two or more courses of intensive combination chemotherapy (e.g., rituximab,
irinotecan hydrochloride, cetuximab, epirubicin hydrochloride [RICE]) as
appropriate according to diagnosis and prior therapy

- Heavily pre-treated CLL patients in whom further combination chemotherapy
is not appropriate may receive single-agent intermediate-dose
cyclophosphamide for 2-3 courses

- No mantle cell or DLC NHL with progressive disease at allograft work-up

- No suitable matched related or unrelated donor available

- Two umbilical cord blood (UCB) units available meeting the following criteria:

- Units and recipient must be ≥ 4/6 HLA-A and -B antigen and DRB1 allele matched

- Each unit must have ≥ 1.5 x 10^7 total nucleated cells/recipient body weight

PATIENT CHARACTERISTICS:

- Karnofsky performance score 70-100%

- Creatinine clearance ≥ 50 mL/min

- Bilirubin < 2.5 mg/dL

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

- Spirometry and corrected DLCO ≥ 50% normal

- LVEF ≥ 40%

- Albumin ≥ 2.5 g/dL

- No active and uncontrolled infection at time of transplantation, including active
infection with Aspergillus or other mold

- No HIV positivity

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 120 days since prior autologous stem cell transplantation

- No more than 60 days since prior chemotherapy

- 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 after transplantation

Outcome Time Frame:

1 Year after transplant

Safety Issue:

No

Principal Investigator

Juliet Barker, MBBS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

06-066

NCT ID:

NCT00387959

Start Date:

July 2006

Completion Date:

September 2014

Related Keywords:

  • Leukemia
  • Lymphoma
  • recurrent mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle 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
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • splenic marginal zone lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021