CD34+ Transplants for Leukemia and Lymphoma

Phase 2

Not yet recruiting

• Conditions: Leukemia, Lymphocytic, Acute; Leukemia, Myeloid, Acute
• Interventions: Radiation: Total Body Irradiation (TBI); Drug: Busulfan; Drug: Thiotepa; Drug: Melphalan; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT05565105
• Lead Sponsor: Guenther Koehne

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-09-28
• Study First Submitted QC: 2022-09-30
• Study First Posted: 2022-10-04
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-21
• Last Update Posted: 2024-11-25
• Study Start: 2025-03
• Primary Completion: 2032-03
• Study Completion: 2032-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen A: TBI/Thiotepa/Cyclophosphamide	Total Body Irradiation (TBI)	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)
Regimen A: TBI/Thiotepa/Cyclophosphamide	Thiotepa	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)
Regimen A: TBI/Thiotepa/Cyclophosphamide	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)
Regimen B: Busulfan/Melphalan/Fludarabine	Busulfan	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
Regimen B: Busulfan/Melphalan/Fludarabine	Melphalan	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
Regimen B: Busulfan/Melphalan/Fludarabine	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).

Trial Locations

Locations (1)

Baptist Health South Florida/Miami Cancer Institute; 🇺🇸 Miami, Florida, United States