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A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for B-Cell Non-Hodgkin Lymphoma Using Zevalin, Fludarabine and Melphalan


Phase 2
18 Years
70 Years
Open (Enrolling)
Both
Graft Versus Host Disease, Leukemia, Lymphoma

Thank you

Trial Information

A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for B-Cell Non-Hodgkin Lymphoma Using Zevalin, Fludarabine and Melphalan


OBJECTIVES:

- To evaluate the safety and efficacy of a preparative regimen of Yttrium-90 (90^Y)-
Labeled Anti-CD20 Monoclonal Antibody (MAb) (yttrium Y 90 ibritumomab tiuxetan) in
combination with Fludarabine (fludarabine phosphate) and Melphalan followed by
Allogeneic Hematopoietic Stem Cell Transplant (APBSCT) for treatment of patients with
B-Cell Low-Grade Non-Hodgkin Lymphoma (LG NHL), Intermediate-Grade Non-Hodgkin Lymphoma
(IG NHL) and Mantle Cell Lymphoma (MCL). II. To evaluate the short- and long-term
complications of this new preparative regimen, including rates of engraftment, Acute
and Chronic Graft-Versus-Host-Disease (GVHD) and infectious complications. III. To
estimate the disease response rate, disease relapse (progression) rate, and non-relapse
mortality rate of this treatment strategy. IV. To perform exploratory studies that seek
to measure/characterize the expression of costimulatory molecules and impact of these
molecules on the natural killer (NK) and T cells of lymphoma patients pre- post-
allogeneic stem cell transplant (ASCT).

OUTLINE:

- REDUCED-INTENSITY CONDITIONING: Patients receive rituximab IV followed by indium In-111
ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV followed by yttrium
Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive
fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. STEM CELL
TRANSPLANTATION: Patients undergo APBSCT on day 0. GVHD PROPHYLAXIS: Patients receive
tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3 and continuing for up
to 6 months with taper. After completion of study treatment, patients are followed up
every 3 months for 1 year and then every 6 months for up to 5 years.


Inclusion Criteria:



- 6/6/human leukocyte antigen (HLA) matched sibling donor or related donor, or
acceptable matched unrelated donor

- Biopsy (Bx) proven diagnosis of LG (including small lymphocytic lymphoma
[SLL]/chronic lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma, marginal zone,
mucosa-associated lymphoid tissue [MALT] lymphoma and follicular lymphoma [FL] grade
1 and 2), IG (FL grade 3 and DLCL) or MCL NHL

- Prior demonstrated monoclonal CD20+ malignant B-Cell population in lymph nodes and/or
BM Bx specimen

- LG NHL; must have relapsed after achieving a complete response (CR) or partial
response (PR) to prior therapy or have never responded to prior therapy, including
chemotherapy and/or MAb therapy

- MCL NHL in any disease state

- Other aggressive B-cell lymphomas (excluding Burkitt lymphoma or Burkitt-like
lymphoma) having had at least one relapse or having been refractory to chemotherapy

- Bone marrow (BM) aspiration and Bx ( =< 42 days prior to imaging dose) which show <
25% lymphomatous involvement of total cellularity; in CLL, peripheral lymphocyte
count < 5000/mm^3

- Salvage chemotherapy/MAbs to reduce BM lymphomatous involvement and reduce disease
bulk allowed

- Normal renal function test with serum creatinine of =< 1.5 mg/dl, or a creatinine
clearance of >= 60 ml/min

- Adequate pulmonary function as measured by forced expiratory volume in one second
(FEV1) > 65% of predicted measured, or a diffusing capacity of carbon monoxide (DLCO)
>= 50% of predicted measured

- Cardiac Ejection fraction of > 50% by Echocardiogram (ECHO) or multi gated
acquisition (MUGA)

- Adequate liver function tests with a bilirubin of =< 1.5 x normal and serum glutamic
oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x
normal

- Negative Human Immunodeficiency Virus (HIV) antibody

- Karnofsky Performance Status (KPS) > 80

- No active Central Nervous System (CNS) disease or prior history of CNS disease

- Involved field External Beam Therapy (EBT) to area excluding lung, heat, liver, and
kidney allowed, but evaluated on a case-by-case basis

- Recovery from last therapy and therapy dose (Y-90 Zevalin) must be >= 4 weeks from
prior systemic chemotherapy

- DONOR: Age < 75 years

- DONOR: HLA genotypically identical related donor or acceptable matched unrelated
donor

- DONOR: Must consent to G-CSF administration and leukapheresis for matched sibling
donor, but for unrelated donor, the donor will sign a standard consent for donation
at their designated donor or collection center

- DONOR: Must have adequate veins for leukapheresis or agree to placement of a Central
Venous Catheter (CVC [femoral, subclavian])

Exclusion Criteria:

- Presence of Human Anti-Zevalin Antibody (HAZA)

- Prior radioimmunotherapy (RIT)

- Prior AHSCT; but prior aHSCT is allowed; prior fractionated total body irradiation
(FTBI) in the conditioning regimen will be evaluated on an individual basis

- Prior malignancy, except for: adequately treated basal cell or squamous cell skin
cancer; adequately treated noninvasive carcinomas; or other cancer from which the
patient has been disease-free for at least 5 years; myelodysplastic syndromes (MDS)
is excluded from this criterion

- Active evidence of Hepatitis B or C infection; hepatitis B surface antigen positive

- Total peripheral lymphocyte count > 5,000/mm^3 if SLL/CLL

- Burkitt lymphoma or Burkitt-like lymphoma

- DONOR: Age < 12 years

- DONOR: Identical twin

- DONOR: Pregnancy

- DONOR: HIV infection

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness or any disease that may preclude the use of
G-CSF (eg, recent thromboembolic event); for unrelated donors, considered ineligible
by National Marrow Donor Program (NMDP) donor evaluation center

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Relapse/progression rate

Outcome Description:

Confidence intervals will be established by calculating the exact 95% confidence limits for a binomial parameter. The product-limit method of Kaplan and Meier will be utilized.

Outcome Time Frame:

At 2 years

Safety Issue:

No

Principal Investigator

Auayporn P. Nademanee, MD

Investigator Role:

Study Chair

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Federal Government

Study ID:

05149

NCT ID:

NCT00577278

Start Date:

January 2007

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • graft versus host disease
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II 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
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I 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
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • Waldenstrom macroglobulinemia
  • contiguous stage II marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • recurrent marginal zone lymphoma
  • stage I marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • B-cell chronic lymphocytic leukemia
  • refractory chronic lymphocytic leukemia
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • stage I mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • contiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • recurrent small lymphocytic lymphoma
  • stage I small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell

Name

Location

City of Hope Medical CenterDuarte, California  91010