Zevalin Before Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

Joseph Tuscano

Status and phase

Active, not recruiting

Phase 2

Conditions

Refractory Non Hodgkin Lymphoma

Relapsed Non Hodgkin Lymphoma

Treatments

Drug: cyclosporine

Procedure: peripheral blood stem cell transplantation

Biological: anti-thymocyte globulin

Radiation: total nodal irradiation

Drug: mycophenolate mofetil

Biological: ibritumomab tiuxetan

Procedure: allogeneic hematopoietic stem cell transplantation

Biological: rituximab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01811368

367905

NCI-2012-02753 (Registry Identifier)

UCDCC#233 (Other Identifier)

Details and patient eligibility

About

This phase II trial studies how well ibritumomab tiuxetan before donor peripheral blood stem cell transplant works in treating patients with relapsed or refractory non-Hodgkin lymphoma. Giving rituximab, antithymocyte globulin, and total-lymphoid irradiation (TLI) before a donor peripheral blood 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. Also, radiolabeled monoclonal antibodies, such as ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor 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 make an immune response against the body's normal cells. Giving rituximab, antithymocyte globulin, and TLI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody before a donor peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.

Full description

PRIMARY OBJECTIVES:

I. To measure the response conversion (progressive disease [PD]/stable disease [SD] to partial response [PR] and complete response [CR]).

SECONDARY OBJECTIVES:

I. To assess the time to engraftment/chimerism. II. To assess the rate of acute and chronic graft-versus-host disease (GVHD). III. To assess toxicity. IV. To determine the overall survival. V. To investigate immune functional and phenotypic analysis. VI. To measure two year event free survival (EFS).

OUTLINE:

CONDITIONING REGIMEN: Patients receive rituximab intravenously (IV) on days -21 and 14, ibritumomab tiuxetan IV on day -14, TLI on days -11 to -7 and -4 to -1, and antithymocyte globulin IV over 4-6 hours on days -11 to -7. Patients also undergo TLI on days -11 to -7 and -4 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) twice daily (BID) or IV on days -3 to 56 with taper to 6 months and mycophenolate mofetil PO BID or IV on days 0-28.

After completion of study treatment, patients are followed up periodically.

Enrollment

20 estimated patients

Sex

All

Ages

19 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically or cytologically confirmed relapsed cluster of differentiation (CD)20+ non-Hodgkin's lymphoma (NHL) (included in this category are follicular grade I, II, III, marginal zone, mantle cell, diffuse large B cell, small lymphocytic lymphoma) and CD20+ Hodgkin's disease for which standard curative therapy does not exist or is no longer effective
Patients must have had at least one prior chemotherapeutic regimen; steroids alone and local radiation do not count as regimens; radiotherapy must have been completed at least 4 weeks prior to entry into the study; Rituxan alone does not count as a regimen; however, Bexxar or Zevalin (ibritumomab tiuxetan) do and patients must have completed radioimmunotherapy (RIT) > 12 months prior to enrollment
Karnofsky performance status of ≥ 60%
Life expectancy of greater than 3 months
Total bilirubin within institutional normal limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
Blood counts no restrictions
Patients who had anything less than a CR (PR, SD or progressive disease) to their last salvage regimen
Ability to understand and the willingness to sign a written informed consent document
Patients fit for non-myeloablative transplantation or best treatment that have an available matched (9/10 or better) related or unrelated donor
Patients who are considered rituximab refractory (defined as progression within 6 months of their last rituximab-containing regimen)

Exclusion criteria

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, rituximab within three months (unless there is evidence of progression), or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include the use of steroids which may continue until two days prior to enrollment
Patients may not be receiving any other investigational agents
Failure to obtain insurance/payment authorization for Zevalin, unless the subject agrees to cover the cost
Patients with known active brain metastases, other neurological disorders/dysfunction or a history of seizure disorder, or other neurological dysfunction should be excluded from this clinical trial because of their poor prognosis
Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month
Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure; left ventricular ejection fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is < 30%
Patients requiring supplementary continuous oxygen; diffusion capacity of the lung of carbon monoxide (DLCO) is not required to be measured, however if it is measured, patient is excluded if DLCO < 35%
Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension
Patients with any of the following liver function abnormalities will be excluded:
- Fulminant liver failure
- Cirrhosis with evidence of portal hypertension or bridging fibrosis
- Alcoholic hepatitis
- Esophageal varices
- A history of bleeding esophageal varices
- Hepatic encephalopathy
- Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
- Ascites related to portal hypertension
- Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
- Symptomatic biliary disease
Pregnant women are excluded from this study
Human immunodeficiency virus (HIV)-positive patients

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

Experimental group

Description:

CONDITIONING REGIMEN: Patients receive rituximab IV on days -21 and 14, ibritumomab tiuxetan IV on day -14, TLI on days -11 to -7 and -4 to -1, and antithymocyte globulin IV over 4-6 hours on days -11 to -7. Patients also undergo TLI on days -11 to -7 and -4 to -1. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO BID or IV on days -3 to 56 with taper to 6 months and mycophenolate mofetil PO BID or IV on days 0-28.

Treatment: