Phase 2
N=52
Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia · Prolymphocytic Leukemia · Recurrent Small Lymphocytic Lymphoma · Refractory Chronic Lymphocytic Leukemia · Stage III Chronic Lymphocytic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT00104858 ↗Enrolled (actual)
52
Serious AEs
7.7%
Results posted
Jul 2019
Primary outcome: Primary: Overall Survival — 34 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Cyclosporine (Drug); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Mycophenolate Mofetil (Drug); Peripheral Blood Stem Cell Transplantation (Procedure); Pharmacological Study (Other); Rituximab (Biological); Total-Body Irradiation (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Mar 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
34 | — |
| SECONDARY Comparison of Survival, Serious Adverse Events, and B-cell and T-cell Immune Reconstitution With Historical Data |
— | — |
| SECONDARY Number of Participants With Relapse/Progression |
1 | — |
| SECONDARY Graft-versus-leukemia Analysis by Mechanism of Disease Resistance in Relapsed or Non-responding Patients and Isolation of Donor Cytotoxic T Lymphocytes Specific for Host Minor Histocompatibility Antigens |
— | — |
| SECONDARY Number of Participants With Grade II-III and III-IV Acute GVHD and Chronic GVHD |
46 | — |
| SECONDARY Number of Participants With Regimen-related Toxicity and Infections |
48 | — |
| SECONDARY Number of Participants With Treatment-related Mortality |
14 | — |
| SECONDARY Rituxan Concentration |
109; 51; 1.3; .03 | — |
| SECONDARY Number of Patients Achieving Complete Response and Partial Response (Overall Response Rate) |
35 | — |
| SECONDARY Donor and Host Polymorphisms of the FCgammaRIIIa Receptor and CD32 and Their Impact on Disease Response and Relapse |
2; 21; 2; 19 | — |
Summary
This phase II trial studies how well fludarabine phosphate with radiation therapy and rituximab followed by donor stem cell infusions work in treating patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with low side effects. Nonmyeloablative stem cell transplants use low doses of chemotherapy (fludarabine phosphate) and radiation to suppress the patient's immune system enough to prevent rejection of the donor's stem cells. Following infusion of donor stem cells, a mixture of the patient's and the donor's stem cells will exist and is called "mixed chimerism". Donor cells will attack the patient's leukemia. This is called the "graft-versus-leukemia" effect. Rituximab will be given 3 days before and three times after infusing stem cells to help in controlling CLL early after transplant till the "graft-versus-leukemia" takes control. Further, rituximab could augment the "graft-versus-leukemia" effect by activating donor immune cells and hence improve disease control. Sometimes the transplanted cells from a donor can also attack the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
Eligibility Criteria
Inclusion Criteria
- Patients with a diagnosis of CLL (or SLL) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL)
- Patients with B-Cell CLL or PLL who:
- Failed to meet National Cancer Institute (NCI) Working Group criteria 2 for complete or partial response after 2 cycles of therapy with regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or with disease relapse within 12 months after completing therapy with a fludarabine (or another nucleoside analog) containing regimen
- Failed FCR or pentostatin/cyclophosphamide/rituximab (PCR) combination chemotherapy at any time point
- Patients with novo or acquired "17p deletion" cytogenetic abnormality; patients should have received induction treatment but could be transplanted in 1st CR
- Patients who have suitable human leukocyte antigen (HLA)-matched related or unrelated donors willing to receive filgrastim (G-CSF), undergo leukapheresis to collect peripheral blood mononuclear cell (PBMC), and to donate stem cells
- RELATED DONORS: When more than one potential donor exists, priority should be given to donors based on HLA identity > cytomegalovirus (CMV) seronegativity > ABO compatibility > sex matching
- Donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1
- Must consent to G-CSF administration and leukapheresis;
- Must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian);
- Only G-CSF mobilized PBMC only will be permitted as a hematopoietic stem cell (HSC) source on this protocol
- UNRELATED DONORS:
- Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades 1.0 to 2.1; Unrelated donors who are prospectively:
- Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
- UNRELATED DONORS: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody screens to class I and II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
- UNRELATED DONORS: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
- UNRELATED DONORS: Only G-CSF mobilized PBMC will be permitted as a HSC source on this protocol
Exclusion Criteria
- Infection with human immunodeficiency virus (HIV)
- Active diagnosis of central nervous system (CNS) involvement with CLL
- Patients unwilling to use contraceptive techniques before and for 12 months after HCT
- Pregnant women or females who are breastfeeding
- The addition of cytotoxic agents for 'cytoreduction' with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning
- Active bacterial or fungal infections unresponsive to medical therapy
- Performance status: Karnofsky score 50 years or there is a history of prior transplant, anthracycline exposure or history of cardiac disease; and poorly controlled hypertension despite multiple antihype
Data sourced from ClinicalTrials.gov (NCT00104858). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.