CD34+ Transplants for Leukemia and Lymphoma

Guenther Koehne

Status and phase: Not yet enrolling; Phase 2

Conditions: Leukemia, Lymphocytic, Acute; Leukemia, Myeloid, Acute

Treatments: Drug: Thiotepa; Drug: Cyclophosphamide; Drug: Busulfan; Drug: Fludarabine; Drug: Melphalan; Radiation: Total Body Irradiation (TBI)

Study type: Interventional

Funder types: Other

Identifiers

NCT05565105

2021-KOE-001

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No 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:

  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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Regimen A: TBI/Thiotepa/Cyclophosphamide

Experimental group

Description:

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)

Treatment:

Radiation: Total Body Irradiation (TBI)

Drug: Cyclophosphamide

Drug: Thiotepa

Regimen B: Busulfan/Melphalan/Fludarabine

Experimental group

Description:

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

Treatment:

Drug: Fludarabine

Drug: Melphalan

Drug: Busulfan