Phase 2
Completed N=87
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies
Hematologic Malignancies
Source: ClinicalTrials.gov NCT01203722 ↗
Enrolled (actual)
87
Serious AEs
1.2%
Results posted
Feb 2026
Primary outcomePrimary: Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD) — 2; 0; 5; 1 Participants
Summary
If transplantation using mismatched unrelated donors or non-first-degree relatives could be performed with an acceptable toxicity profile, an important unmet need would be served. Towards this goal, the current study extends our platform of nonmyeloablative, partially HLA-mismatched bone marrow transplant (BMT) and Peripheral Blood Stem Cell Transplant (PBSCT) to the use of such donors, investigating up to several postgrafting immunosuppression regimens that incorporate high-dose Cy. Of central interest is the incorporation of sirolimus into this postgrafting immunosuppression regimen.
The primary goal for phase 1 is to identify a transplant regimen associated with acceptable rates of severe acute GVHD and NRM by Day 100 and for phase 2 estimate the 6-month probability of survival without having had acute grade III- IV GVHD or graft failure.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD) |
2; 0; 5; 1 | — |
| PRIMARY Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM) |
2; 0; 1; 0 | — |
| PRIMARY 6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure. |
51; 1; 26; 2 | — |
| SECONDARY Progression-free Survival |
48; 1; 30; 2 | — |
| SECONDARY Event-free Survival |
47; 1; 26; 2 | — |
| SECONDARY Overall Survival |
47; 1; 26; 2 | — |
| SECONDARY Cumulative Incidence of Progression or Relapse |
4; 0; 3; 0 | — |
| SECONDARY Cumulative Incidence of Non-relapse Mortality (NRM). |
7; 0; 4; 0 | — |
| SECONDARY Cumulative Incidence of Acute Grade II-IV GVHD. |
2; 0; 1; 0 | — |
| SECONDARY Cumulative Incidence of Acute Grade III-IV GVHD |
0; 0; 0; 0 | — |
| SECONDARY Cumulative Incidence of Chronic GVHD |
0; 0; 0; 0 | — |
| SECONDARY Cumulative Incidence of Graft Failure |
2; 0; 0; 1 | — |
| SECONDARY Cumulative Incidence of Neutrophil Recovery |
54; 1; 30; 2 | — |
| SECONDARY Cumulative Incidence of Platelet Recovery |
54; 1; 29; 2 | — |
| SECONDARY Cumulative Incidence of Donor Engraftment |
53; 1; 30; 2 | — |
| SECONDARY Cumulative Incidence of Failure Free Survival |
53; 1; 30; 2 | — |
Eligibility Criteria
Patient Inclusion Criteria:
- Patient age 0.5-75 years
- Absence of a suitable related or unrelated bone marrow donor who is molecularly matched at HLA-A, B, Cw, DRB1, and DQB1.
- Absence of a suitable partially HLA-mismatched (haploidentical), first-degree related donor. Donors who are homozygous for the CCR5delta32 polymorphism are given preference.
- Eligible diagnoses:
- Relapsed or refractory acute leukemia in second or subsequent remission, with remission defined as 3 abnormalities], inv(3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7
- Primary refractory disease
- ALL (leukemia and/or lymphoma) with at least one of the following:
- Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL rearrangement
- Clear evidence of hypodiploidy
- Primary refractory disease
- Biphenotypic leukemia
- MDS with at least one of the following poor-risk features:
- Poor-risk cytogenetics (7/7q minus or complex cytogenetics)
- IPSS score of INT-2 or greater
- Treatment-related MDS
- MDS diagnosed before age 21 years
- Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
- Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
- Interferon- or imatinib-refractory CML in first chronic phase, or non-blast crisis CML beyond first chronic phase.
- Philadelphia chromosome negative myeloproliferative disease.
- Chronic myelomonocytic leukemia.
- Juvenile myelomonocytic leukemia.
- Low-grade non-Hodgkin lymphoma (including SLL and CLL) or plasma cell neoplasm that has:
- progressed after at least two prior therapies (excluding single agent rituximab and single agent steroids), or
- in the case of lymphoma undergone histologic conversion;
- patients with transformed lymphomas must have stable disease or better.
- Poor-risk CLL or SLL as follows:
- 11q deletion disease that has progressed after a combination chemotherapy regimen,
- 17p deletion disease,
- or histologic conversion;
- patients with transformed lymphomas must have stable disease or better.
- Aggressive non-Hodgkin lymphoma as follows, provided there is stable disease or better to last therapy:
- NK or NK-T cell lymphoma, hepatosplenic T-cell lymphoma, or subcutaneous panniculitic T-cell lymphoma, blastic/ blastoid variant of mantle cell lymphoma
- Hodgkin or aggressive non Hodgkin lymphoma that has failed at least one multiagent regimen, and the patient is either ineligible for autologous BMT or autologous BMT is not recommended.
- Eligible subtypes of aggressive non-Hodgkin lymphoma include:
- mantle cell lymphoma
- follicular grade 3 lymphoma
- diffuse large B-cell lymphoma or its subtypes, excluding primary CNS lymphoma
- primary mediastinal large B-cell lymphoma
- large B-cell lymphoma, unspecified
- anaplastic large cell lymphoma, excluding skin-only disease
- Burkitt's lymphoma or atypical Burkitt's lymphoma (high-grade B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's), in complete remission
- Patients with CLL, SLL, or prolymphocytic leukemia must have 25%, unless cleared by a cardiologist
- Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air
- ECOG performance status 60
Patient Exclusion Criteria:
- Not pregnant or breast-feeding.
- No uncontrolled bacterial, viral, or fungal infection.
- Note: HIV-infected patients are potentially eligible. Eligibility of HIV-infected patients will be determined on a case-by-case basis.
- No previous allogeneic BMT (syngeneic BMT permissible).
- Active extramedullary leukemia or known active CNS involvement by malignancy. Such disease treated into remission is permitted.
Donor Inclusion Criteria:
- Potential donors consist of:
- Unrela
Data sourced from ClinicalTrials.gov (NCT01203722). 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.