Graft Versus Host Disease, Leukemia, Lymphoma
Conditions
Keywords
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
Brief summary
RATIONALE: Giving monoclonal antibody therapy, radioimmunotherapy, and chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor that do not exactly match the patient's blood, are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and sirolimus before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects and how well giving indium In 111 ibritumomab tiuxetan and yttrium y 90 ibritumomab tiuxetan together with rituximab, fludarabine, melphalan, and donor stem cell transplant works in treating patients with B-cell non-Hodgkin lymphoma.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the safety and efficacy of a preparative regimen of Yttrium-90 (90\^Y)- labeled anti-cluster of differentiation (CD)20 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. 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 a subset of lymphoma patients pre- post- allogeneic stem cell transplant (ASCT) and the stem cell product from a portion of sibling donors. OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive rituximab intravenously (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.
Interventions
DRUGsirolimus
Given PO
DRUGtacrolimus
Given PO or IV
BIOLOGICALrituximab
Given IV
DRUGfludarabine phosphate
Given IV
DRUGmelphalan
Given IV
PROCEDUREallogeneic hematopoietic stem cell transplantation
Undergo APBSCT
RADIATIONindium In 111 ibritumomab tiuxetan
Given IV
RADIATIONyttrium Y 90 ibritumomab tiuxetan
Given IV
OTHERlaboratory biomarker analysis
Correlative Studies
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse/Progression Rate at Two Years | From the initial treatment to the last disease assessment, up to two years | The primary endpoint was 2-year cumulative incidence of relapse/progression (RP), defined as time from alloHCT to disease recurrence or progression. Cumulative incidences for RP was generated in a competing-risk setting, given that death events were competing events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at Two Years | From the initial treatment to the last disease assessment, up to two years | Overall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. |
| Progression-free Survival at Two Years | From the initial treatment to the last disease assessment, up to two years | Progression-free survival (PFS) was measured from initial treatment to disease progression or death from any cause, whichever came first. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.4 mCi 90Y-Ibritumomab Tiuxetan 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. Patients undergo APBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper.
rituximab: Given IV fludarabine phosphate: Given IV melphalan: Given IV sirolimus: Given PO tacrolimus: Given PO or IV allogeneic hematopoietic stem cell transplantation: Undergo APBSCT indium In 111 ibritumomab tiuxetan: Given IV yttrium Y 90 ibritumomab tiuxetan: Given IV | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | 0.4 mCi 90Y-Ibritumomab Tiuxetan |
|---|---|
| Age, Continuous | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 41 |
| other Total, other adverse events | 41 / 41 |
| serious Total, serious adverse events | 28 / 41 |
Outcome results
Primary
Relapse/Progression Rate at Two Years
The primary endpoint was 2-year cumulative incidence of relapse/progression (RP), defined as time from alloHCT to disease recurrence or progression. Cumulative incidences for RP was generated in a competing-risk setting, given that death events were competing events.
Time frame: From the initial treatment to the last disease assessment, up to two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.4 mCi 90Y-Ibritumomab Tiuxetan | Relapse/Progression Rate at Two Years | 20 percentage of cumulative incidence |
Secondary
Overall Survival at Two Years
Overall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula.
Time frame: From the initial treatment to the last disease assessment, up to two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.4 mCi 90Y-Ibritumomab Tiuxetan | Overall Survival at Two Years | 63 percentage of survival probability |
Secondary
Progression-free Survival at Two Years
Progression-free survival (PFS) was measured from initial treatment to disease progression or death from any cause, whichever came first. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula.
Time frame: From the initial treatment to the last disease assessment, up to two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.4 mCi 90Y-Ibritumomab Tiuxetan | Progression-free Survival at Two Years | 61 percentage of survival probability |