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

NCT04282174 | Withdrawn Phase 2 FDA Device

• 1 other identifier: 2019-KOE-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 Fractionation system is a method that positively selects CD34+ progenitor cells from PBSC by immunoadsorption of cells binding on anti CD34 monoclonal antibody to paramagnetic beads, which can then be isolated by passage through a magnetized column and released by agitation of beads. Two conditioning regimens have been used successfully with an alternative similar system, isolex, which is no longer being manufactured.

Conditions

Hematologic Diseases; Hematologic Malignancy; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (4)

• Assess the change of incidence and severity of chronic GvHD

  To assess the incidence and severity of chronic GvHD following T cell depleted, CD34+ progenitor cell enriched transplants fractionated by the CliniMACS system.

  6 months, 1 year, 2 years

• Assess the change of incidence and severity of acute GvHD

  To assess the incidence and severity of acute GvHD following T cell depleted, CD34+ progenitor cell enriched transplants fractionated by the CliniMACS system.

  6 months, 1 year, 2 years

• Assess the change of incidence of non-relapse mortality

  To assess the incidence of non-relapse mortality (transplant-related mortality) following each cytoreduction regimen and a transplant fractionated by the CliniMACS system.

  6 months, 1 year, 2 years

• Estimate the probability change of survival and disease-free survival (DFS)

  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.

  6 months, 1 year, 2 years

Secondary Outcomes (2)

• Determine the proportion of patients receiving optimal CD34+; CD3+

  6 months, 1 year, 2 years

• Correlate doses of CD34+ progenitors and CD3+ T cells with engraftment

  6 months, 1 year, 2 years

Study Arms (2)

Regimen A

EXPERIMENTAL

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)

Device: CliniMACS; Procedure: Bone Marrow Transplant; Drug: Hyperfractionated Total Body Irradiation; Drug: Thiotepa; Drug: Cyclophosphamide

Regimen B

EXPERIMENTAL

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.

Device: CliniMACS; Procedure: Bone Marrow Transplant; Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine

Interventions

CliniMACS DEVICE

allogeneic Human leukocyte antigen-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system

Regimen A; Regimen B

Bone Marrow Transplant PROCEDURE

Bone Marrow Transplant will come from either an HLA matched related sibling or HLA un-related donor

Regimen A; Regimen B

Hyperfractionated Total Body Irradiation DRUG

Hyperfractionated Total Body Irradiation is administered at a dose rate of \< 20 cGy/minute. Doses of 125 cGy/fraction are administered at a minimum interval of 4 hours between fractions, three times/day for a total of 11 or 12 doses (1375 or 1500 cGy) over 4 days (Day -9, -8, -7 and -6).

Regimen A

Thiotepa DRUG

Thiotepa: 5mg/kg/day IV over approximately 4 hr. daily x 2 (Day -5 and Day -4). If scheduling of transplant harvests requires, the dose of Thiotepa may be administered as a single dose of 10mg/kg/day x 1.

Regimen A

Cyclophosphamide DRUG

Cyclophosphamide: 60 mg/kg/day I V over approximately 30 min daily x 2 days (d -3 and -2). Cyclophosphamide dosing will be adjusted if patient is \> 125% of ideal body w eight and will be calculated based on adjusted ideal body weight, as per MCI standard of care guidelines.

Regimen A

Busulfan DRUG

0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified

Regimen B

Melphalan DRUG

Melphalan 70mg/m2/day x 2 days IV over 30 minutes. Dose should be adjusted if patient is \> 125% ideal body weight and should be calculated on adjusted ideal body weight per MCI standard of care guidelines. Melphalan will be administered on Days - 7 and -6 for multiple myeloma patients.

Regimen B

Fludarabine DRUG

Fludarabine 25mg/m2/days x 5 days IV over 30 minutes. Fludarabine may be adjusted in the case of renal toxicity. In select cases in which the peripheral blood stem cells must be harvested a day later than requested due to a scheduling issue with the donor or Stem Cell Processing Laboratory.

Regimen B

Eligibility Criteria

• Age: Up to 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• Secondary AML in 1st remission
• AML in 1st relapse or 2nd remission
• 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
• 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.
• 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.
• 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.
• Chronic myelomonocyte leukemia: CMML-1 and CMML-2.
• Multiple Myeloma with disease in the following categories:
• Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.
• 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.
• Patient's age includes from birth on to \< 74 years old.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baptist Health South Florida: lead

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Related Links

• MCI - Website

MeSH Terms

Conditions

Hematologic Diseases; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bone Marrow Transplantation; Thiotepa; Cyclophosphamide; Busulfan; Melphalan; fludarabine

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplasms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Guenther Koehne, MD

  Miami Cancer Institute (MCI) at Baptist Health, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The two myeloablative conditioning regimens are: Regimen A: Hyperfractionated Total Body Irradiation/Thiotepa/Cyclophosphamide: 100 patients Regimen B: Busulfan/Melphalan/Fludarabine: 100 patients It is anticipated that the accrual will last five years. Patients will be followed for two years following transplantation.

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 24, 2020
• Study Start: September 1, 2022
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: September 27, 2022

Record last verified: 2022-09

Locations

US (1)