Abatacept as GVHD Prophylaxis Phase 2
Graft vs Host Disease · Malignancy
Bottom Line
View on ClinicalTrials.gov: NCT01743131 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Abatacept (Drug); placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 6+ yrs
- Sex
- All
- Sponsor
- Boston Children's Hospital
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Cumulative Incidence of Severe aGVHD at Day +100 Post-transplant |
6.8; 14.8; 2.2; 30.2 | — |
| SECONDARY A Cumulative Incidence of Relapse, Non-relapse Mortality, Acute GVHD Grade III-IV, cGVHD Requiring Systemic Therapy, Overall Survival and GRFS Will be Computed. |
24.6; 23.4; 11.6; 23.7; 18.5; 18.6 | — |
| SECONDARY Percentage of Participants With Severe (Grade III-IV) aGVHD Free Survival (GFS) up to Day +180 |
93.2; 82; 97.7; 58.7 | — |
| SECONDARY Rate of Severe (Grade III-IV) aGVHD (Based on Adjudicated aGVHD Events) up to Day +180 |
6.8; 14.8; 2.2; 32.1 | — |
Summary
Eligibility Criteria
Inclusion Criteria
- Must be at least 6 years old and weigh 20 kg.
- Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. The use of mismatched donors in which disparity is only in the host versus graft direction (because of recipient homozygosity) is discouraged because of the potentially heightened risk for graft rejection. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
- All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
- Must have a high risk hematologic malignancy as defined below:
- Acute myeloid leukemia (AML).
- Myelodysplastic syndrome
(i) Adult patients (≥21 years) must meet criteria for intermediate, high or very high-risk disease based on the World Health Organization classification based prognostic scoring system.
Intermediate risk (2 points), high risk (3-4 points), very high risk (4-5 points)
- RA = refractory anemia, RARS = refractory anemia with ringed sideroblasts, RCMD = refractory cytopenia with multilineage dysplasia, RCMD-RS = refractory cytopenia with multilineage dysplasia and ringed sideroblasts, RAEB-1 = refractory anemia with excess of blasts-1 (5-9% blasts), RAEB-2 = refractory anemia with excess of blasts-2 (10-19% blasts).
- *Karyotype: Good = normal, -Y, del(5q), del(20q), Poor = complex (≥ 3 abnormalities), chromosome 7 anomalies, Intermediate = other abnormalities.
- *RBC transfusion requirement = having ≥ 1 RBC transfusion every 8 weeks over a 4-month period.
(ii) Pediatric patients with MDS, regardless of subtype, will be eligible.
(c) Acute lymphoblastic leukemia (ALL). (i) Given the poor prognosis of adults (≥21 years) with ALL, adults in 1st or greater complete remission will be eligible.. CR is defined as an M1 marrow ( 1% residual marrow blasts by flow cytometry at the end of induction.
- >0.01% residual marrow blasts by flow cytometry at the end of consolidation.
- Early T-Cell Precursor (ETP) phenotype
- In 2nd complete remission with B-lineage disease after a marrow relapse occurring less than 36 months from diagnosis.
- In 2nd complete remission with T-lineage disease or Ph+ disease after a marrow relapse occurring at any time.
- In a 2nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than 18 months from diagnosis.
- In 3rd or greater complete remission after a marrow or extramedullary relapse
(d) Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission (CR) or partial remission (PR). Cr will be defined as an M1 marrow ( 1.5 cm in greatest transverse diameter that has regressed by > 75% in sum of the products of the greatest perpendicular diameters (SPD), or any residual lesions in organs that have decreased by > 75%, with a negative PET scan, negative bone marrow and CSF.
(g) Peripheral T cell lymphoma (PTCL).
(h) Chronic lymphocytic leukemia (CLL) (i) Newly diagnosed disease with 17p- (ii) Disease beyond first CR that has been treated with a fludarabine containing regimen.
(i) Chronic myelomonocytic leukemia.
(j) Atypical (BCR-ABL negative) chronic myelogenous leukemia
(k) Hodgkin lymphoma that has recurred or progressed after an autologous BMT. Disease must be chemosensitive; salvage chemotherapy must produce at least a partial response.
(l) Non-Hodgkin lymphomas that has recurred or progressed after an autologous BMT.
Exclusion Criteria
Data sourced from ClinicalTrials.gov (NCT01743131). 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.