Yttrium Y 90 Ibritumomab Tiuxetan, Rituximab, Indium In-111 Ibritumomab Tiuxetan, Fludarabine, Melphalan, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin Lymphoma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Graft Versus Host Disease Leukemia Lymphoma |
Biological: rituximab Drug: fludarabine phosphate Drug: melphalan Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Radiation: indium In 111 ibritumomab tiuxetan Radiation: yttrium Y 90 ibritumomab tiuxetan |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for B-Cell Non-Hodgkin Lymphoma Using Zevalin, Fludarabine and Melphalan |
- Relapse/progression rate [ Time Frame: At 2 years ] [ Designated as safety issue: No ]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.
- Relapse-free survival [ Time Frame: 5 years from transplant ] [ Designated as safety issue: No ]The product-limit method of Kaplan and Meier will be utilized. Will consider univariate Cox models.
- Progression-free survival [ Time Frame: 5 years from transplant ] [ Designated as safety issue: No ]The product-limit method of Kaplan and Meier will be utilized. Will consider univariate Cox models.
- Toxicity and safety of treatment regimen [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]Will be summarized in terms of type, severity (by National Cancer Institute [NCI] Common Toxicity Criteria [CTC] and nadir or maximum values for the laboratory measure) and time of onset. Analyses will be conducted to evaluate acute and chronic GVHD and infectious complications.
- Duration of response [ Time Frame: 5 years from transplant ] [ Designated as safety issue: No ]
- Time-to-progression (TTP) [ Time Frame: 5 years from transplant ] [ Designated as safety issue: No ]
- Non-relapse mortality [ Time Frame: 5 years from transplant ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 46 |
| Study Start Date: | January 2007 |
| Estimated Primary Completion Date: | June 2020 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (chemo, monoclonal antibody therapy, transplant)
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 PO and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper.
|
Biological: rituximab
250 mg/m2 possibly given on Day -21, Day -14 and Day +1 from stem cell transplant depending on measured rituximab level. 250 mg/m2 given on Day +8 from stem cell transplant.
Drug: fludarabine phosphate
25 mg/m2 daily for 5 days beginning on Day -9 from stem cell transplant.
Drug: melphalan
140 mg/m2 given on Day -4 from stem cell transplant.
Drug: sirolimus
12 mg loading dose given on Day -3 from stem cell transplant, then 4 mg oral single daily dose given with adjustments based upon weekly measured serum levels
Drug: tacrolimus
0.02 mg/kg iv daily from Day -3 of stem cell transplantation. Once oral intake resumes, switch to oral at 2-3X the iv dose.
Procedure: allogeneic hematopoietic stem cell transplantation
Allogeneic peripheral blood stem cells given at Day 0 after completion of non-myeloablative conditioning.
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Allogeneic peripheral blood stem cells given at Day 0 after completion of non-myeloablative conditioning.
Radiation: indium In 111 ibritumomab tiuxetan
5 mCi given on Day -21 from stem cell transplantation
Radiation: yttrium Y 90 ibritumomab tiuxetan
0.4 mCi/kg, not to exceed 32 mCi, given on Day -14 from stem cell transplantation
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations| United States, California | |
| City of Hope Medical Center | Recruiting |
| Duarte, California, United States, 91010-3000 | |
| Contact: Clinical Trials Office 800-826-4673 | |
| Study Chair: | Auayporn P. Nademanee, MD | City of Hope Medical Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT00577278 History of Changes |
| Other Study ID Numbers: | 05149, P01CA030206, CHNMC-05149, CDR0000579136, NCI-2010-01230 |
| Study First Received: | December 19, 2007 |
| Last Updated: | March 6, 2013 |
| Health Authority: | United States: Federal Government United States: Institutional Review Board |
Keywords provided by City of Hope Medical Center:
|
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 |
Additional relevant MeSH terms:
|
Graft vs Host Disease Leukemia Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Immune System Diseases Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Melphalan Fludarabine Fludarabine monophosphate Rituximab |
Sirolimus Everolimus Tacrolimus Antibodies, Monoclonal Vidarabine Myeloablative Agonists Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013