CD34+ Enriched Transplants From HLA-Compatible Patients With Hematologic Malignancies

• Status: Not yet recruiting
• Trial end date: 2030-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase II trial testing disease-specific myeloablative conditioning regimens for preparatory cytoreduction of patients receiving allogeneic HLA-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells (PBSC) depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system. The CliniMACS Fractionation system is a method that positively selects CD34+ progenitor cells from PBSC by immunoadsorption of cells binding on anti CD34 monoclonal antibody to paramagnetic beads, which can then be isolated by passage through a magnetized column and released by agitation of beads. Two conditioning regimens have been used successfully with an alternative similar system, isolex, which is no longer being manufactured.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Baptist Health South Florida
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Melphalan; Thiotepa; Vidarabine

Criteria

Inclusion Criteria:

Malignant conditions or other life-threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:

1. Acute myeloid leukemia (AML) in 1st remission - for patients who is AML does not have 'good risk' cytogenetic features (i.e. t8:21, t 15: 17, inv16).

2. Secondary AML in 1st remission

3. AML in 1st relapse or 2nd remission

4. Acute lymphoblastic leukemia (ALL) / Chronic Lymphocytic Leukemia (CLL) in pt remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission

5. Chronic myelogenous leukemia (CML) failing to respond to or not tolerating Imatinib or Dasatinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.

6. Non-Hodgkin's lymphoma with chemo responsive disease in any of the following categories:

1. Intermediate or high-grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.

2. Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.

7. Myelodysplastic syndrome (MDS): RA/RARS/RCMA with high-risk cytogenetic features or transfusion dependence, as well as RAEB-1 and RAEB-2 and Acute Myelogenous Leukemia (AML) evolved from MDS.

8. Chronic myelomonocyte leukemia: CMML-1 and CMML-2.

9. Multiple Myeloma with disease in the following categories:

1. Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.

2. Patients with high-risk cytogenetics at diagnosis must have achieved at least a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del l7p, t4; 14 and/or t 4; 16 by Fluorescence in situ hybridization (FISH) and/or del l3 by karyotyping.

The following inclusion criteria are also required:

• Patient's age includes from birth on to < 74 years old.

• Patients may be of either gender or any ethnic background.

• Patients must have a Karnofsky (adult) Performance Status of at least 70%

• Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be 50% and must improve with exercise.

Hepatic: < 3x ULN AST and: s 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree). Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval e.g. patients with PNH, Gilbert's disease or other hemolytic disorders.

Renal: serum creatinine: s; 1.2 mg/di or if serum creatinine is outside the normal range, then CrCl > 40 ml/m in (measured or calculated/estimated).

Pulmonary: asymptomatic or if symptomatic, DLCO 50% of predicted (corrected for hemoglobin).

Each patient must be willing to participate as a research subject and must sign an informed consent form.

Donor Inclusion Criteria

• Each donor must meet criteria outlined by institutional guidelines

• Donor should agree to undergo general anesthesia and bone marrow harvest collection if PBSC yield is inadequate or otherwise not transplantable for whatever reason.

Exclusion Criteria:

Subject Exclusion Criteria

• Female patients who are pregnant or breast-feeding

• Active viral, bacterial or fungal infection

• Patient seropositive for HI V-I /II; HTLV -I /II

• Presence of leukemia in the CNS.

Donor Exclusion Criteria

• If donors do not meet institutional guidelines, exclusion will be considered.