Phase 2
Completed N=44
Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant
Source: ClinicalTrials.gov NCT01252667 ↗Enrolled (actual)
44
Serious AEs
0.0%
Results posted
Apr 2020
Primary outcomePrimary: Part 1: Number of Participants With Dose Limiting Toxicities (DLT) — 0; 0; 0; 0 Participants
Summary
This phase II trial studies the side effects and how well clofarabine works when given together with low-dose total-body irradiation (TBI) in treating patients with acute myeloid leukemia (AML) undergoing donor peripheral blood stem cell transplant (PBSCT). Giving chemotherapy and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem 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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicities (DLT) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Relapsed Disease |
0; 0; 0; 0; 0; 3 | — |
| SECONDARY Number of Participants Surviving Progression-free. |
0; 2; 1; 0; 0; 21 | — |
| SECONDARY Number of Participants Surviving Overall |
0; 2; 1; 0; 0; 22 | — |
| SECONDARY Number of Non-Relapse Mortalities (NRM) |
0; 1; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants Who Graft Rejected. |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Prognostic Significance of Cytogenetic and Genetic Markers |
— | — |
| SECONDARY Number of Participants With Minimal Residual/Recurring Disease (MRD) Post-transplant |
0; 2; 0; 0; 0; 6 | — |
| SECONDARY Pharmacokinetics (PK) of Clofarabine |
0.53; 0.37; 0.29; 0.40; 0.50 | — |
Eligibility Criteria
Inclusion Criteria
- Patients age >= 55 years with AML OR patients age 0 ("high risk") will be enrolled during Part 1; patients with all Relapse Risk Scores will be enrolled during Part 2 (low risk group terminated August 2014)
- HLA-identical related or HLA-matched unrelated donor available
- A signed informed consent form or minor assent form
- DONOR: FHCRC matching allowed will be grade 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
- DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; 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; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class 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
- DONOR: Patient and donor pairs homozygous at a mismatched allele 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
- DONOR: Peripheral blood stem cells (PBSC) only will be permitted as a HSC source on this protocol
Exclusion Criteria
- AML French-American-British (FAB) M3 in first complete remission (CR1)
- Active AML involvement of the central nervous system (CNS) with disease refractory to intrathecal chemotherapy
- Presence of circulating leukemic blasts in the peripheral blood detected by standard morphology
- Patients who are human immunodeficiency virus (HIV)+ (HIV+ patients registered at Fred Hutchinson Cancer Research Center [FHCRC] should be offered treatment on Protocol 1410)
- Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
- Left ventricular ejection fraction 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
- Serum creatinine should be within normal limits as specified by institutional guidelines; for patients with serum creatinine > upper limit of normal, a 24-hour creatinine clearance will be performed and should be equal to or more than the lower limit of normal
- Karnofsky score < 60 or Lansky score < 50
- Patients with poorly controlled hypertension and on multiple antihypertensives
- Females who are pregnant or breastfeeding
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
- 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
- Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Patients with active bacterial or fungal infections unresponsive to medical therapy
- DONOR: Marrow donors
- DONOR: Donors who are HIV-positive and/or medical conditions that would r
Data sourced from ClinicalTrials.gov (NCT01252667). 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. Informational only — not medical advice.