Phase 2 N=47 Treatment

Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia (BMT CTN 0303)

Leukemia, Myelocytic, Acute

Bottom Line

View on ClinicalTrials.gov: NCT00201240 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Nov 2014

Primary outcome: Primary: Probability of Disease-free Survival (DFS) at 6 Months Post-transplant (Death or Relapse Will be Considered Events for This Endpoint) — 81.8 percentage of patients

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: CD34+ selection with CliniMACS device (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Primary completion: Dec 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Probability of Disease-free Survival (DFS) at 6 Months Post-transplant (Death or Relapse Will be Considered Events for This Endpoint)	81.8	—
SECONDARY Leukemia Relapse	20.6; 23.7	—
SECONDARY Neutrophil Engraftment	12	—
SECONDARY Platelet Engraftment	16	—
SECONDARY Graft Failure	0; 1	—
SECONDARY Acute Graft Versus Host Disease (GVHD)	22.7; 4.5	—
SECONDARY Chronic Graft Versus Host Disease (GVHD)	19.0; 6.8	—
SECONDARY Transplant Related Mortality	14; 20; 23.2	—
SECONDARY Determination of Infusional Toxicity	—	—
SECONDARY Disease-free Survival (DFS)	81.8; 66; 53	—
SECONDARY Overall Survival	77; 56	—
SECONDARY CD34+ and CD3+ Cell Doses	7.9; 6.6	—
SECONDARY Post-transplant Lymphoproliferative Disorder (PTLD)	8	—

Summary

This study is a single arm Phase II, multicenter trial. It is designed to determine whether the anticipated endpoints for a T cell depleted transplant arm of a planned prospective randomized trial comparing T cell depleted and unmodified hematopoietic allografts are likely to be achieved in a multicenter study conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN or Network). The study population is patients with acute myeloid leukemia (AML) in first or second morphologic complete remission. The enrollment is 45 patients. Based on published results of unmodified transplants from HLA-matched siblings applied to patients with AML in first or second morphologic complete remission, a significant improvement in results with a graft modified as specified in this protocol would be expected if disease-free survival (DFS) at 6 months was greater than 75%, the true incidence of transplant-related mortality at 1 year was less than 30%, and the DFS rate at 2 years was greater 70% for patients transplanted in first remission and less than 60% for patients transplanted in second remission. Additional secondary endpoints include the following: graft failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease (GVHD). Additionally, the trial will have target specific doses of CD34+ progenitors and CD3+ T cells to be obtained following fractionation with the CliniMACS system. Based on the results of this trial, a Phase III trial comparing T cell depleted peripheral blood stem cell transplants (PBSCT) with unmanipulated bone marrow or unmanipulated PBSCT will be designed.

Eligibility Criteria

Inclusion Criteria

Patients with AML with or without prior history of myelodysplastic syndrome based on the World Health Organization criteria at the following stages:
First morphologic complete remission (CR)
Second morphologic CR
If prior history of central nervous system (CNS) involvement, no evidence of active CNS leukemia during the pre-transplant evaluation (no evidence of leukemic blasts in cerebrospinal fluid)
First or second CR was achieved after no more than two cycles of induction (or re-induction for patients in second CR) chemotherapy
No more than 6 months elapsed from documentation of CR to transplant for patients in first CR, or 3 months for patients in second CR.
A 6/6 HLA antigen (A, B, DRB1)-compatible sibling donor; the match may be determined at serologic level for HLA-A and HLA-B loci; DRB1 must be matched at least at low-resolution using DNA typing techniques; HLA-C will be typed at the serologic level, but not included in the match algorithm
Karnofsky performance status greater than 70%
Life expectancy greater than 8 weeks
Diffusing capacity of the lung for carbon monoxide (DLCO) of at least 40% (corrected for hemoglobin) with no symptomatic pulmonary disease
Left ventricular ejection fraction (LVEF) by Multi Gated Acquisition Scan (MUGA) or echocardiogram greater than 40%
Serum creatinine greater than 2 mg/dL, bilirubin greater than 2 mg/dL, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at least 3 times the upper limit of normal at time of enrollment
Willingness of both the patient and the donor to participate

Exclusion Criteria

M3-AML (acute promyelocytic leukemia) in first CR
Acute leukemia following blast transformation of prior chronic myelogenous leukemia (CML) or other myeloproliferative disease
M4Eo-AML with inv 16 in first CR
AML with t(8;21) in first CR
Participation in other clinical trials that involve investigational drugs or devices except with permission from the Medical Monitor
Evidence of active Hepatitis B or C infection or evidence of cirrhosis
HIV positive
Uncontrolled diabetes mellitus
If proven or probable invasive fungal infection, infection must be controlled; patients may be on prophylactic anti-fungal agents, but are not permitted to be on anti-fungal agents for therapeutic purposes (i.e., active treatment for disease)
Uncontrolled viral or bacterial infection (currently taking medication without clinical improvement)
Documented allergy to iron dextran or murine proteins
Pregnant or breastfeeding; women of childbearing age must avoid becoming pregnant while in the study
Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00201240). 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.