Clinical trial NCT00425802: Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-23
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving rituximab before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects and how well giving chemotherapy and radiation therapy together with rituximab and donor stem cell transplant works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.


Eligibility 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

Primary outcomes:
measure: Overall Survival at 1 Year
timeFrame: 1 year
Secondary outcomes:
measure: Time to Neutrophil Engraftment
timeFrame: 2 years
measure: Time to Platelet Engraftment
timeFrame: 1 year
measure: Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days
timeFrame: 100 days
measure: Incidence of Chronic GVHD at 1 Year
timeFrame: 1 year
measure: Immune Reconstruction/CD4+ Count at 3 Months
timeFrame: 3 months
measure: Response to Treatment
timeFrame: 2 years
measure: Immune Reconstruction/CD4+ Count at 6 Months
timeFrame: 6 months
measure: Immune Reconstruction/CD4+ Count at 1 Year
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Hugo R. Castro-Malaspina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Juliet Barker, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Craig Moskowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sauter CS, Lechner L, Scordo M, Zheng J, Devlin SM, Fleming SE, Castro-Malaspina H, Moskowitz CH. Pretransplantation fluorine-18-deoxyglucose--positron emission tomography scan lacks prognostic value in chemosensitive B cell non-hodgkin lymphoma patients undergoing nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Jun;20(6):881-4. doi: 10.1016/j.bbmt.2014.02.009. Epub 2014 Feb 15.