HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies

NCT01119066 | Completed Phase 2 Results

• 1 other identifier: 10-050
• Study Type: interventional
• Target: 422
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out the effects of using a system called CliniMACS to remove Tcells from blood stem cells. Removing T-cells may help stop a side effect called Graft-Versus-Host Disease (GVHD). Some studies have been done with CliniMACS, but the Food and Drug Administration (FDA) has not yet approved it.

Conditions

Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Multiple Myeloma

Keywords

Leukemia; Multiple Myeloma; radiation; Thiotepa; cyclophosphamide; fludarabine; Clofarabine; CliniMACS device; GCSF; 10-050

Outcome Measures

Primary Outcomes (6)

• The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens.

  3 years

• Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System.

  Standard BMT-CTN and IBMTR systems clinical criteria as defined by Rowlings, et al will be used to establish and grade acute GvHD. Chronic GvHD will be diagnosed and graded according to the criteria of Sullivan (CIBMTR).

  3 years

• Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System.

  3 years

• Survival and Disease-free Survival (DFS)

  at 6 months post transplant

• Survival and Disease-free Survival (DFS)

  1 year post transplant

• Survival and Disease-free Survival (DFS)

  2 years post transplant

Secondary Outcomes (3)

• Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg.

  Up to 3 years

• Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells

  3 years

• Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment

  3 years

Study Arms (4)

Total Body Irradiation, Thiotepa and Cyclophosphamide

EXPERIMENTAL

Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)

Radiation: total body irradiation; Drug: Thiotepa; Drug: Cyclophosphamide; Procedure: (CliniMACS) T-cell depleted PBSC Transplant

Busulfan, Melphalan and Fludarabine

EXPERIMENTAL

Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5)

Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine; Procedure: (CliniMACS) T-cell depleted PBSC Transplant

Clofarabine, Melphalan and Thiotepa

EXPERIMENTAL

Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1)

Drug: Thiotepa; Drug: Melphalan; Drug: Clofarabine; Procedure: (CliniMACS) T-cell depleted PBSC Transplant

Melphalan, Fludarabine and Thiotepa

EXPERIMENTAL

Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1)

Drug: Thiotepa; Drug: Melphalan; Procedure: (CliniMACS) T-cell depleted PBSC Transplant

Interventions

total body irradiation RADIATION

dose of 1375-1500 cGy

Total Body Irradiation, Thiotepa and Cyclophosphamide

Thiotepa DRUG

5 mg/kg/day x 2 or 10 mg/kg/day x 1

Clofarabine, Melphalan and Thiotepa; Melphalan, Fludarabine and Thiotepa; Total Body Irradiation, Thiotepa and Cyclophosphamide

Cyclophosphamide DRUG

60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated).

Total Body Irradiation, Thiotepa and Cyclophosphamide

Busulfan DRUG

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

Busulfan, Melphalan and Fludarabine

Melphalan DRUG

70mg/m2/day x 2

Busulfan, Melphalan and Fludarabine; Clofarabine, Melphalan and Thiotepa; Melphalan, Fludarabine and Thiotepa

Fludarabine DRUG

25mg/m2/ day x 5

Busulfan, Melphalan and Fludarabine

Clofarabine DRUG

20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval)

Clofarabine, Melphalan and Thiotepa

(CliniMACS) T-cell depleted PBSC Transplant PROCEDURE

Busulfan, Melphalan and Fludarabine; Clofarabine, Melphalan and Thiotepa; Melphalan, Fludarabine and Thiotepa; Total Body Irradiation, Thiotepa and Cyclophosphamide

Eligibility Criteria

• Age: Up to 69 Years
• Sex: all
• Healthy Volunteers: No
• 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:
• AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16).
• Secondary AML in 1st remission
• AML in 1st relapse or \> than or = to 2nd remission
• ALL/CLL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL \> than or = to 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-Hodgkins lymphoma with chemoresponsive 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/RCMD with high risk cytogenetic features or transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation and/or unable to enroll onto protocol IRB 08-008.
• Chronic myelomonocytic 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 a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by karyotyping.
• Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily transfused congenital hemoglobinopathies).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Multiple Myeloma; Leukemia

Interventions

Whole-Body Irradiation; Thiotepa; Cyclophosphamide; Busulfan; Melphalan; fludarabine; Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; 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; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Richard O'Reilly, MD
• Organization: Memorial Sloan Kettering Cancer Center

oreillyr@MSKCC.ORG

646-888-2157

Study Officials

• Richard O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 4, 2010
• First Posted: May 7, 2010
• Study Start: May 3, 2010
• Primary Completion: March 30, 2021
• Study Completion: March 30, 2021
• Last Updated: August 5, 2022
• Results First Posted: August 5, 2022

Record last verified: 2021-05

Locations

US (1)