CD34+ Transplants for Leukemia and Lymphoma

Sponsor

Baptist Health South Florida (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05565105

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute Leukemia, Lymphocytic, Acute	Radiation: Total Body Irradiation (TBI) Drug: Thiotepa Drug: Cyclophosphamide Drug: Busulfan Drug: Melphalan Drug: Fludarabine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2030

Anticipated Study Completion Date :

Jan 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen A: TBI/Thiotepa/Cyclophosphamide 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) 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). Other Names: Thioplex Drug: Cyclophosphamide Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m^2 x 5 if cyclophosphamide is contraindicated Other Names: Cytoxan
Experimental: Regimen B: Busulfan/Melphalan/Fludarabine 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 Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Other Names: Busulfex Drug: Melphalan Melphalan: 70 mg/m^2/day x 2 Other Names: Alkeran Drug: Fludarabine Fludarabine: 25 mg/m^2/day x 5 Other Names: Fludara

Arm

Intervention/Treatment

Experimental: Regimen A: TBI/Thiotepa/Cyclophosphamide

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)

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).

Other Names:

Thioplex

Drug: Cyclophosphamide

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

Other Names:

Cytoxan

Experimental: Regimen B: Busulfan/Melphalan/Fludarabine

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

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

Other Names:

Busulfex

Drug: Melphalan

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

Other Names:

Alkeran

Drug: Fludarabine

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

Other Names:

Fludara

Outcome Measures

Primary Outcome Measures

Incidence rate of graft versus host disease (GvHD) [Two years]
Incidence of acute and chronic GvHD
Severity of disease [Two years]
Severity of the adverse events will be reported based on the CTCAE Version 5.
Incidence of transplant-related mortality (TRM) [Two years]
TRM includes fatal complications resulting from the allogeneic transplant and/ or treatment regimens such as graft failure, GvHD, hemorrhages, and infections.
Change in overall survival (OS) [Six months, one year, two years]
OS is defined as time from transplant to death or last follow-up.
Change in disease free survival (DFS) [Six months, one year, two years]
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.

Secondary Outcome Measures

Proportion of patients optimal and suboptimal doses [Two years]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.