CD34+ Transplants for Leukemia and Lymphoma

NCT05565105 | Not Yet Recruiting Phase 2 DMC FDA Device

• 1 other identifier: 2021-KOE-001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Acute

Keywords

Stem Cell Transplant

Outcome Measures

Primary Outcomes (5)

• Incidence rate of graft versus host disease (GvHD)

  Incidence of acute and chronic GvHD

  Two years

• Severity of disease

  Severity of the adverse events will be reported based on the CTCAE Version 5.

  Two years

• 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

• Change in overall survival (OS)

  OS is defined as time from transplant to death or last follow-up.

  Six months, one year, two years

• 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 Outcomes (1)

• Proportion of patients optimal and suboptimal doses

  Two years

Study Arms (2)

Regimen A: TBI/Thiotepa/Cyclophosphamide

EXPERIMENTAL

Patients in enrolled in Regimen A will receive the following: * Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding * Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day * Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m\^2 x 5 days may be substituted)

Radiation: Total Body Irradiation (TBI); Drug: Thiotepa; Drug: Cyclophosphamide

Regimen B: Busulfan/Melphalan/Fludarabine

EXPERIMENTAL

Patients in enrolled in Regimen B will receive the following: * Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease * Melphalan, 70 mg/m\^2/day x 2 days via IV infusion over 30 minutes daily * Fludarabine, 25 mg/m\^2/day x 5 days via IV infusion over 30 minutes daily

Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine

Interventions

Cyclophosphamide DRUG

Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m\^2 x 5 if cyclophosphamide is contraindicated

Also known as: Cytoxan

Regimen A: TBI/Thiotepa/Cyclophosphamide

Total Body Irradiation (TBI) RADIATION

Hyper-fractioned TBI is administered by a linear accelerator at a dose rate of \< 15 cGy/minute.

Regimen A: TBI/Thiotepa/Cyclophosphamide

Thiotepa DRUG

Thiotepa: 5 mg/kg/day IV over approximately 4 hours daily x 2 (Day -5 and Day -4).

Also known as: Thioplex

Regimen A: TBI/Thiotepa/Cyclophosphamide

Busulfan DRUG

Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics

Also known as: Busulfex

Regimen B: Busulfan/Melphalan/Fludarabine

Melphalan DRUG

Melphalan: 70 mg/m\^2/day x 2

Also known as: Alkeran

Regimen B: Busulfan/Melphalan/Fludarabine

Fludarabine DRUG

Fludarabine: 25 mg/m\^2/day x 5

Also known as: Fludara

Regimen B: Busulfan/Melphalan/Fludarabine

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Guenther Koehne: lead

Study Sites (1)

Baptist Health South Florida/Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Related 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.

  PMID: 15753458 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 12091376 BACKGROUND

• 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.

  PMID: 17717135 BACKGROUND

Related Links

• Miami Cancer Institute

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Whole-Body Irradiation; Thiotepa; Cyclophosphamide; Busulfan; Melphalan; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Guenther Koehne, MD, PhD

  Baptist Health South Florida/Miami Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guenther Koehne, MD, PhD

CONTACT

786-596-2000; GuentherK@baptisthealth.net

Claudia Torralbas, RN

CONTACT

786-596-2000; claudiatorr@baptisthealth.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 4, 2022
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2033
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)