CD34+ Transplants for Leukemia and Lymphoma

Official title

A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Leukemia or Lymphoma

Overview

This study will evaluate whether processing blood stem cell transplants using an investigational device (the CliniMACS system) results in less complications for patients undergoing transplant for treatment of a blood malignancy (cancer) or blood disorder.

Interventions

• Radiation Total Body Irradiation (TBI)
  Hyper-fractioned TBI is administered by a linear accelerator at a dose rate of \< 15 cGy/minute.
• Drug Thiotepa
  Thiotepa: 5 mg/kg/day IV over approximately 4 hours daily x 2 (Day -5 and Day -4).
• Drug Cyclophosphamide
  Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m\^2 x 5 if cyclophosphamide is contraindicated
• Drug Busulfan
  Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics
• Drug Melphalan
  Melphalan: 70 mg/m\^2/day x 2
• Drug Fludarabine
  Fludarabine: 25 mg/m\^2/day x 5

Primary outcome measures

• Incidence rate of graft versus host disease (GvHD) [Time frame: Two years]
• Severity of disease [Time frame: Two years]
• Incidence of transplant-related mortality (TRM) [Time frame: Two years]
• Change in overall survival (OS) [Time frame: Six months, one year, two years]
• Change in disease free survival (DFS) [Time frame: Six months, one year, two years]

Secondary outcome measures (1)

• Proportion of patients optimal and suboptimal doses [Time frame: Two years]

Eligibility 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:

• AML in 1st remission - for patients who is AML does not have 'good risk' cytogenetic features (i.e. t8:21, t 15: 17, inv16).
• Secondary AML in 1st remission
• AML in 1st relapse or 2nd remission
• ALL/CLL in patient remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission
• 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.
• Non-Hodgkin's lymphoma with chemo responsive disease in any of the following categories:

• 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.
• Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
• Chronic myelomonocyte leukemia: CMML-1 and CMML-2.

The following inclusion criteria are also required:

• Patient's age includes from ≥18 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/dL or if serum creatinine is outside the normal range, then CrCl > 30 ml/min (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.

Exclusion criteria

• Female patients who are pregnant or breast-feeding
• Active viral, bacterial or fungal infection
• Patient seropositive for HIV-I /II; HTLV -I /II
• Presence of leukemia in the CNS

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Baptist Health South Florida/Miami Cancer Institute — Miami

Publications

• Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.12 PMID 15753458
• Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, Bader P, Schlegel PG, Greil J, Stachel D, Herzog RJ, Niethammer D. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant. 2001 Apr;27(8):777-83. doi: 10.1038/sj.bmt.1702996. PMID 11477433
• Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteyza J, Ferra C, Zuazu J, Caballero D, Bargay J, Carvalhais A, Diez JL, Espigado I, Alegre A, Rovira M, Campilho F, Odriozola J, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E; Spanish Group for Allogeneic Peripheral Blood Transplantation (Grupo Espanol de Trasplante Hemopoyetico) and Instituto Portugues de Oncolog PMID 12091376
• Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC, Perales MA, Collins N, Cisek C, Chiu M, van den Brink MR, O'Reilly RJ, Papadopoulos EB. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood. 2007 Dec 15;110(13):4552-9. doi: 10.1182/blood PMID 17717135

Identifiers

NCT: NCT05565105 · 2021-KOE-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗