CD34+ Enriched Transplants From HLA-Compatible Patients With Hematologic Malignancies

Phase 2

Withdrawn

• Conditions: Hematologic Malignancy; Hematologic Diseases; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia
• Interventions: Device: CliniMACS; Procedure: Bone Marrow Transplant; Drug: Hyperfractionated Total Body Irradiation; Drug: Busulfan; Drug: Thiotepa; Drug: Melphalan; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT04282174
• Lead Sponsor: Baptist Health South Florida

Brief Summary

This is a Phase II trial testing disease-specific myeloablative conditioning regimens for preparatory cytoreduction of patients receiving allogeneic HLA-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells (PBSC) depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system. The CliniMACS ...

Detailed Description

For this trial, patients will be put into one of two myeloablative conditioning regimens, based on their disease, stage of disease, and dose of radiation accumulated in the course of treatment. Approximately twenty-four to forty-eight hours after completion of each conditioning regimen, patients will receive a transplant of a CD34+ progenitor cell-enriched, ...

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: 2020-02-17
• Study First Submitted QC: 2020-02-21
• Study First Posted: 2020-02-24
• Status Verified: 2022-09
• Study Start: 2022-09
• Last Update Submitted: 2022-09-26
• Last Update Posted: 2022-09-27
• Primary Completion: 2030-03-01
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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. Acute myeloid leukemia (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. Acute lymphoblastic leukemia (ALL) / Chronic Lymphocytic Leukemia (CLL) in pt remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission

5. Chronic myelogenous leukemia (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. Myelodysplastic syndrome (MDS): RA/RARS/RCMA with high-risk cytogenetic features or transfusion dependence, as well as RAEB-1 and RAEB-2 and Acute Myelogenous Leukemia (AML) evolved from MDS.

8. Chronic myelomonocyte leukemia: CMML-1 and CMML-2.

9. Multiple Myeloma with disease in the following categories:

   1. Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.
   2. Patients with high-risk cytogenetics at diagnosis must have achieved at least a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del l7p, t4; 14 and/or t 4; 16 by Fluorescence in situ hybridization (FISH) and/or del l3 by karyotyping.

The following inclusion criteria are also required:

• Patient's age includes from birth on 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/di or if serum creatinine is outside the normal range, then CrCl > 40 ml/m in (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.

Donor Inclusion Criteria

• Each donor must meet criteria outlined by institutional guidelines
• Donor should agree to undergo general anesthesia and bone marrow harvest collection if PBSC yield is inadequate or otherwise not transplantable for whatever reason.

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Exclusion Criteria

Subject Exclusion Criteria

• Female patients who are pregnant or breast-feeding
• Active viral, bacterial or fungal infection
• Patient seropositive for HI V-I /II; HTLV -I /II
• Presence of leukemia in the CNS.

Donor Exclusion Criteria

• If donors do not meet institutional guidelines, exclusion will be considered.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen B	CliniMACS	Regimen B: Busulfan/Melphalan/Fludarabine: Busulfan 0.8mg/kg/dose every six hours x 10-12 doses (depending on disease), Melphalan 70mg/m2/day x 2 and Fludarabine 25mg/m2/day x 5.
Regimen B	Bone Marrow Transplant	Regimen B: Busulfan/Melphalan/Fludarabine: Busulfan 0.8mg/kg/dose every six hours x 10-12 doses (depending on disease), Melphalan 70mg/m2/day x 2 and Fludarabine 25mg/m2/day x 5.
Regimen A	CliniMACS	Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: Hyperfractionated total body irradiation to dose of 1375cGy fractions at 4-6 hour intervals three times a day for a total of 11 or 12 doses depending on age and disease risk, followed by Thiotepa 5mg/kg/day x 2 (or 10mg/kg/day x 1) and cyclophosphamide 60mg/kg/day x 2 (or Fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Regimen A	Bone Marrow Transplant	Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: Hyperfractionated total body irradiation to dose of 1375cGy fractions at 4-6 hour intervals three times a day for a total of 11 or 12 doses depending on age and disease risk, followed by Thiotepa 5mg/kg/day x 2 (or 10mg/kg/day x 1) and cyclophosphamide 60mg/kg/day x 2 (or Fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Regimen A	Hyperfractionated Total Body Irradiation	Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: Hyperfractionated total body irradiation to dose of 1375cGy fractions at 4-6 hour intervals three times a day for a total of 11 or 12 doses depending on age and disease risk, followed by Thiotepa 5mg/kg/day x 2 (or 10mg/kg/day x 1) and cyclophosphamide 60mg/kg/day x 2 (or Fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Regimen A	Thiotepa	Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: Hyperfractionated total body irradiation to dose of 1375cGy fractions at 4-6 hour intervals three times a day for a total of 11 or 12 doses depending on age and disease risk, followed by Thiotepa 5mg/kg/day x 2 (or 10mg/kg/day x 1) and cyclophosphamide 60mg/kg/day x 2 (or Fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Regimen A	Cyclophosphamide	Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: Hyperfractionated total body irradiation to dose of 1375cGy fractions at 4-6 hour intervals three times a day for a total of 11 or 12 doses depending on age and disease risk, followed by Thiotepa 5mg/kg/day x 2 (or 10mg/kg/day x 1) and cyclophosphamide 60mg/kg/day x 2 (or Fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Regimen B	Busulfan	Regimen B: Busulfan/Melphalan/Fludarabine: Busulfan 0.8mg/kg/dose every six hours x 10-12 doses (depending on disease), Melphalan 70mg/m2/day x 2 and Fludarabine 25mg/m2/day x 5.
Regimen B	Melphalan	Regimen B: Busulfan/Melphalan/Fludarabine: Busulfan 0.8mg/kg/dose every six hours x 10-12 doses (depending on disease), Melphalan 70mg/m2/day x 2 and Fludarabine 25mg/m2/day x 5.
Regimen B	Fludarabine	Regimen B: Busulfan/Melphalan/Fludarabine: Busulfan 0.8mg/kg/dose every six hours x 10-12 doses (depending on disease), Melphalan 70mg/m2/day x 2 and Fludarabine 25mg/m2/day x 5.

Primary Outcome Measures

Name	Time	Method
Assess the change of incidence and severity of acute GvHD	6 months, 1 year, 2 years	To assess the incidence and severity of acute GvHD following T cell depleted, CD34+ progenitor cell enriched transplants fractionated by the CliniMACS system.
Assess the change of incidence and severity of chronic GvHD	6 months, 1 year, 2 years	To assess the incidence and severity of chronic GvHD following T cell depleted, CD34+ progenitor cell enriched transplants fractionated by the CliniMACS system.
Assess the change of incidence of non-relapse mortality	6 months, 1 year, 2 years	To assess the incidence of non-relapse mortality (transplant-related mortality) following each cytoreduction regimen and a transplant fractionated by the CliniMACS system.
Estimate the probability change of survival and disease-free survival (DFS)	6 months, 1 year, 2 years	To estimate the probability of survival and disease-free survival (DFS) at 6 months, 1 year and 2 years post-transplant for each disease-targeted cytoreduction regimen when used with a T-cell depleted graft fractionated by the CliniMACS system.

Secondary Outcome Measures

Name	Time	Method
Correlate doses of CD34+ progenitors and CD3+ T cells with engraftment	6 months, 1 year, 2 years	To correlate doses of CD34+ progenitors and CD3+ T cells with engraftment, graft vs. host disease and non-relapse mortality.
Determine the proportion of patients receiving optimal CD34+; CD3+	6 months, 1 year, 2 years	To determine the proportion of patients receiving optimal CD34+ (\>5x 106/kg) and CD3+ (\< 5 x104/kg) cell doses the proportion recurring suboptimal doses (\<3 x 106/kg) CD34+ cells; and the proportion of patients receiving CD3+ T-cell doses \>5 x 104/kg.

Trial Locations

Locations (1)

Miami Cancer Institute at Baptist Health, Inc.; 🇺🇸 Miami, Florida, United States