Phase 2
N=28
Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib
Adult Acute Lymphoblastic Leukemia in Remission · Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 · Blastic Phase · Childhood Acute Lymphoblastic Leukemia in Remission · Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
Bottom Line
View on ClinicalTrials.gov: NCT00036738 ↗Enrolled (actual)
28
Serious AEs
7.1%
Results posted
Aug 2017
Primary outcome: Primary: Relapse Free Survival — 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cyclosporine (Drug); Dasatinib (Drug); Fludarabine Phosphate (Drug); Imatinib Mesylate (Drug); Mycophenolate Mofetil (Drug); Nilotinib (Drug); Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Peripheral Blood Stem Cell Transplantation (Procedure); Therapeutic Allogeneic Lymphocytes (Biological); Total-Body Irradiation (Radiation)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Jul 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relapse Free Survival |
3 | — |
| SECONDARY Leukemia-free Survival |
19; 17; 13; 11; 11; 10 | — |
| SECONDARY Overall Survival |
26; 24; 19; 17; 16; 13 | — |
| SECONDARY Transplant-related Mortality |
3 | — |
| SECONDARY Transplant-related Mortality |
3 | — |
Summary
This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.
Eligibility Criteria
Inclusion Criteria
- Patients = 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
- 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
- Only G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol
Exclusion Criteria
- Central nervous system (CNS) involvement with leukemia refractory to intrathecal chemotherapy; prior to HSCT (all patients must receive a diagnostic lumbar puncture (LP) with intrathecal (IT) chemotherapy as per standard practice)
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
- Females who are pregnant or breastfeeding
- Patients who are human immunodeficiency virus (HIV)-positive
- Patients with poorly controlled hypertension despite multiple antihypertensives
- Adults: Karnofsky score 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction 3 mg/dL, or symptomatic biliary disease
- Creatinine levels more than 2.2 X's the upper limit of normal (ULN) at the laboratory where the analysis was performed
- Patients with active bacterial or fungal infections unresponsive to medical therapy
- For patients receiving dasatinib or nilotinib, baseline corrected QT interval (QTc) (Fridericia's method) prolongation greater than 500 msec
- RELATED DONORS:
- Identical twin
- Infection with HIV
- Inability to achieve adequate venous access
- Known allergy to G-CSF
- Current serious system illness
- Bone marrow (BM) donors
- HLA-MATCHED UNRELATED DONORS:
- BM donors
- Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC
Data sourced from ClinicalTrials.gov (NCT00036738). 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.