CD34+ Transplants for Leukemia and Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Leukemia or Lymphoma

Conditions
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Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute

Intervention / Treatment
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* Radiation: Total Body Irradiation (TBI)
* Drug: Thiotepa
* Drug: Cyclophosphamide
* Drug: Busulfan
* Drug: Melphalan
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A: TBI/Thiotepa/Cyclophosphamide<br>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)<br>* Hyper-fractioned TBI is administered by a linear accelerator at a dose rate of < 15 cGy/minute.<br>Drug: Thiotepa<br>* Thiotepa: 5 mg/kg/day IV over approximately 4 hours daily x 2 (Day -5 and Day -4).<br>* Other names: Thioplex;Drug: Cyclophosphamide<br>* Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m^2 x 5 if cyclophosphamide is contraindicated<br>* Other names: Cytoxan;|
| Experimental: Regimen B: Busulfan/Melphalan/Fludarabine<br>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<br>* Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics<br>* Other names: Busulfex;Drug: Melphalan<br>* Melphalan: 70 mg/m^2/day x 2<br>* Other names: Alkeran;Drug: Fludarabine<br>* Fludarabine: 25 mg/m^2/day x 5<br>* Other names: Fludara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cell Transplant