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

NCT ID: NCT01119066

Last Updated: 2022-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 422 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-03
• Study Completion Date: 2021-03-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Total Body Irradiation, Thiotepa and Cyclophosphamide

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)

Group Type: EXPERIMENTAL

total body irradiation

Intervention Type: RADIATION

dose of 1375-1500 cGy

Thiotepa

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

(CliniMACS) T-cell depleted PBSC Transplant

Intervention Type: PROCEDURE

Busulfan, Melphalan and Fludarabine

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)

Group Type: EXPERIMENTAL

Busulfan

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

70mg/m2/day x 2

Fludarabine

Intervention Type: DRUG

25mg/m2/ day x 5

(CliniMACS) T-cell depleted PBSC Transplant

Intervention Type: PROCEDURE

Clofarabine, Melphalan and Thiotepa

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)

Group Type: EXPERIMENTAL

Thiotepa

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

70mg/m2/day x 2

Clofarabine

Intervention Type: 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)

(CliniMACS) T-cell depleted PBSC Transplant

Intervention Type: PROCEDURE

Melphalan, Fludarabine and Thiotepa

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)

Group Type: EXPERIMENTAL

Thiotepa

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

70mg/m2/day x 2

(CliniMACS) T-cell depleted PBSC Transplant

Intervention Type: PROCEDURE

Interventions

total body irradiation

dose of 1375-1500 cGy

Intervention Type: RADIATION

Thiotepa

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Busulfan

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

Intervention Type: DRUG

Melphalan

70mg/m2/day x 2

Intervention Type: DRUG

Fludarabine

25mg/m2/ day x 5

Intervention Type: DRUG

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)

Intervention Type: DRUG

(CliniMACS) T-cell depleted PBSC Transplant

Intervention Type: PROCEDURE

Eligibility Criteria

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 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:

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.

• 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:

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 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).
• Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk patients (60 patients/treatment arm) except for Regimen D, which will include 30 patients/treatment arm, all of which will be poor risk by virtue of risks of relapse and/or transplant related mortality.
• Standard risk patients will include eligible patients, as defined above, who are receiving transplants as treatment for MDS in RA//RARS/RCMD, AML in 1st or 2nd remission, ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial Response, or 1st Partial Response or CML in the first chronic phase or 1st remission.
• All other patients, including those with treatment related malignancies and/or those who have AML derived from MDS, will have received extensive prior chemo/radiotherapy and, therefore, will be considered to be at poor risk of conditioning and transplant related morbidities, and potentially transplant related mortality. Patients with life threatening non-malignant genetic and acquired disorders will also, by virtue of their history of, optional transfusions and/or infection be considered poor risk. Stopping rules for non-relapse related mortality in these heavily treated patients are, therefore, slightly less stringent than patients in the poor risk transplant groups. Stopping rules for the principal endpoints of graft failure and GvHD are the same for all groups.

• Patient's age includes from birth on to < 70 years old.
• Patients may be of either gender or any ethnic background.
• Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or = to 70%
• Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or = to 50% and must improve with exercise.

Hepatic: < 3x ULN AST and ≤ to 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 are also eligible with PI approval e.g. patients with PNH, Gilbert's disease or other hemolytic disorders.

Renal: serum creatinine < than or = to 1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary: asymptomatic or if symptomatic, DLCO > or = to 50% of predicted (corrected for hemoglobin)

• Each patient must be willing to participate as a research subject and must sign an informed consent form.

• 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.

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.

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

• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard O'Reilly, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

10-050

Identifier Type: -

Identifier Source: org_study_id