search
Back to results

A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
fludarabine phosphate
melphalan
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
indium In 111 ibritumomab tiuxetan
yttrium Y 90 ibritumomab tiuxetan
laboratory biomarker analysis
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemo, monoclonal antibody therapy, transplant)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
December 19, 2007
Last Updated
March 6, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00577278
Brief Title
A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan
Official Title
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for B-Cell Non-Hodgkin Lymphoma Using Zevalin, Fludarabine and Melphalan
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 3, 2007 (Actual)
Primary Completion Date
May 30, 2019 (Actual)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Lymphoma
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemo, monoclonal antibody therapy, transplant)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
sirolimus
Other Intervention Name(s)
AY 22989, Rapamune, rapamycin, SLM
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Other Intervention Name(s)
FK 506, Prograf
Intervention Description
Given PO or IV
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo APBSCT
Intervention Type
Radiation
Intervention Name(s)
indium In 111 ibritumomab tiuxetan
Other Intervention Name(s)
IDEC-In2B8
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 ibritumomab tiuxetan
Other Intervention Name(s)
90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative Studies
Primary Outcome Measure Information:
Title
Relapse/Progression Rate at Two Years
Description
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
Secondary Outcome Measure Information:
Title
Overall Survival at Two Years
Description
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
Title
Progression-free Survival at Two Years
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Mei, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan

We'll reach out to this number within 24 hrs