Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

Stanford University

Status and phase

Completed

Phase 2

Conditions

Mantle-cell Lymphoma

Leukemia, Mast-Cell

Treatments

Drug: Anti-thymoglobulin, rabbit (ATG, rabbit ATG)

Drug: Cyclosporine

Drug: Hydrocortisone

Drug: Granisetron

Procedure: Total lymphoid irradiation

Drug: Acetaminophen

Drug: Mycophenylate mofetil

Drug: Diphenhydramine

Drug: Solumedrol

Drug: Filgrastim

Drug: Rituximab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00186628

SPO (Other Identifier)

BMT172 (Other Identifier)

96160 (Other Identifier)

P01CA049605 (U.S. NIH Grant/Contract)

IRB-02372

Details and patient eligibility

About

To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)

Full description

To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).

Enrollment

36 patients

Sex

All

Ages

18 to 76 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Recipient Inclusion Criteria:

Between 18 and 76 years of age
Chronic lymphocytic leukemia (CLL):
- Unmutated IgG VH gene status
- Mutated IgG VH genes (> 2% nucleotide change compared to somatic sequence)
- Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT).

(Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.)

Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT.
Adequate renal (Cr < 2.4 mg/dL) and hepatic (Bilirubin < 3.0 mg/dL, Aspartate aminotransferase (AST) < 100 IU) function.
Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
All subjects must provide written informed consent

Donor Inclusion Criteria:

Genotypically or phenotypically human leukocyte antigen (HLA)-identical.
Age < 76 unless cleared by institutional PI
Capable of giving written, informed consent.
Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis

Recipient Exclusion Criteria:

Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ)
Pregnancy
Lactating
Serious uncontrolled infection
HIV seropositivity
Hepatitis B or C seropositivity
Cardiac function: ejection fraction < 40% or uncontrolled cardiac failure
Pulmonary: Diffusing capacity - carbon monoxide (DLCO) < 50% predicted
Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST > 100
Renal: creatinine > 2.4
Karnofsky performance score ≤ 60%
Patients with poorly controlled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 90 repeatedly).
Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.
Inability to comply with the allogeneic transplant treatment.
Uncontrolled central nervous system (CNS) involvement with disease

Donor Exclusion Criteria:

Identical twin to subject
Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days
Serious medical or psychological illness
Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
HIV seropositivity

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

36 participants in 1 patient group

Prophylactic Rituximab

Experimental group

Description:

Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)

Treatment: