CD34+ Transplants for Leukemia and Lymphoma

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05565105
• Other study ID #: 2021-KOE-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: June 2031

Study information

• Verified date: April 2024
• Source: Baptist Health South Florida
• Contact: Guenther Koehne, MD, PhD
• Phone: 786-596-2000
• Email: GuentherK[@]baptisthealth.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 2031
• Est. primary completion date: June 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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. 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. ALL/CLL in patient remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission

5. 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. 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Acute
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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).
• Cyclophosphamide
Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m^2 x 5 if cyclophosphamide is contraindicated
• Busulfan
Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics
• Melphalan
Melphalan: 70 mg/m^2/day x 2
• Fludarabine
Fludarabine: 25 mg/m^2/day x 5

Locations

Country	Name	City	State
United States	Baptist Health South Florida/Miami Cancer Institute	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Guenther Koehne

Country where clinical trial is conducted

United States, 

References & Publications (4)

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: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7. — View Citation

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. — View Citation

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-2007-06-093880. Epub 2007 Aug 23. — View Citation

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 Oncologia-Porto. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood. 2002 Jul 15;100(2):724-7. doi: 10.1182/blood-2001-11-0057. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of graft versus host disease (GvHD)	Incidence of acute and chronic GvHD	Two years
Primary	Severity of disease	Severity of the adverse events will be reported based on the CTCAE Version 5.	Two years
Primary	Incidence of transplant-related mortality (TRM)	TRM includes fatal complications resulting from the allogeneic transplant and/ or treatment regimens such as graft failure, GvHD, hemorrhages, and infections.	Two years
Primary	Change in overall survival (OS)	OS is defined as time from transplant to death or last follow-up.	Six months, one year, two years
Primary	Change in disease free survival (DFS)	DFS is defined as the minimum time interval of times to relapse/recurrence, to death or to the last follow- up, from the time of transplant.	Six months, one year, two years
Secondary	Proportion of patients optimal and suboptimal doses	The proportion of patients receiving optimal cell doses (CD34+: >5x 10^6/kg and CD3+: < 5 x10^4/kg) and suboptimal doses (CD34+: <3 x 10^6/kg and CD3+: >5 x 10^4/kg).	Two years