Planned Donor Lymphocyte Infusion (DLI) After Allogeneic Stem Cell Transplantation (SCT) - Full Text View

Purpose

The goal of this clinical research study is to learn what dose of a kind of immune cell called T-lymphocytes (T-cells) given as a donor infusion about 8-9 weeks after a stem cell transplant has the best results. The safety of this treatment will also be studied. This will be tested in patients with leukemia, MDS, lymphoma, Hodgkin disease, and multiple myeloma. These results are measured as helping to control the disease without severe graft-versus-host disease (GvHD). GvHD is when transplanted donor tissue attacks the tissues of the recipient's body.

Fludarabine, melphalan, and alemtuzumab are commonly given before stem cell transplants:

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
Melphalan is designed to bind to the DNA of cells, which may cause cancer cells to die.
Alemtuzumab is designed to weaken the immune system and reduce the risk of rejection of the transplant and graft-vs-host disease (GvHD).

The donor infusion of T-cells is designed to help restore the immune system after the transplant, cause an immune reaction against the cancer, and reduce the risk of the cancer coming back.

Condition	Intervention	Phase
Leukemia Lymphoma Myeloma Myeloproliferative Diseases	Drug: Fludarabine Drug: Melphalan Drug: Alemtuzumab Procedure: Stem Cell Infusion Drug: Tacrolimus Drug: Methotrexate Drug: G-CSF Procedure: Low Dose Donor T-Cells Procedure: High Dose Donor T-Cells	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 2 Study of Planned Donor Lymphocyte Infusion After Reduced Intensity Allogeneic Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hodgkin Disease Leukemia Lymphoma Multiple Myeloma

Drug Information available for: Methotrexate Melphalan Melphalan hydrochloride Methotrexate sodium Fludarabine Fludarabine phosphate Tacrolimus Filgrastim Lenograstim Granulocyte colony-stimulating factor Alemtuzumab

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Success Rate [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
Success rate defined as alive, engrafted without grade 3 or 4 GvHD or relapse at day 100 post allotx.

Secondary Outcome Measures:

Disease Free Survival (DFS) [ Time Frame: 3 , 6, and 12 months ] [ Designated as safety issue: Yes ]
Disease free survival (DFS) defined as interval between day of transplant and day of death or disease progression.

Estimated Enrollment:	56
Study Start Date:	February 2012
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Low Dose Donor T-Cells Fludarabine 40 mg/m2 by vein on Day -6 to -3. Melphalan 140 mg/m2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.	Drug: Fludarabine 40 mg/m2 by vein on Day -6 to -3. Other Names: Fludarabine Phosphate Fludara Drug: Melphalan 140 mg/m2 by vein on Day -2. Other Name: Alkeran Drug: Alemtuzumab 50 mg by vein on Day -1. Other Names: CAMPATH-1H Campath Procedure: Stem Cell Infusion Reduced intensity stem cell transplant on Day 0. Drug: Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Other Name: Prograf Drug: Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. Drug: G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days. Other Names: Filgrastim NeupogenTM Procedure: Low Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64.
Experimental: High Dose Donor T-Cells Fludarabine 40 mg/m2 by vein on Day -6 to -3. Melphalan 140 mg/m2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.	Drug: Fludarabine 40 mg/m2 by vein on Day -6 to -3. Other Names: Fludarabine Phosphate Fludara Drug: Melphalan 140 mg/m2 by vein on Day -2. Other Name: Alkeran Drug: Alemtuzumab 50 mg by vein on Day -1. Other Names: CAMPATH-1H Campath Procedure: Stem Cell Infusion Reduced intensity stem cell transplant on Day 0. Drug: Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Other Name: Prograf Drug: Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. Drug: G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days. Other Names: Filgrastim NeupogenTM Procedure: High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64.

Arms

Assigned Interventions

Experimental: Low Dose Donor T-Cells

Fludarabine 40 mg/m2 by vein on Day -6 to -3. Melphalan 140 mg/m2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.

Drug: Fludarabine

40 mg/m2 by vein on Day -6 to -3.

Other Names:

Fludarabine Phosphate
Fludara

Drug: Melphalan

140 mg/m2 by vein on Day -2.

Other Name: Alkeran

Drug: Alemtuzumab

50 mg by vein on Day -1.

Other Names:

CAMPATH-1H
Campath

Procedure: Stem Cell Infusion

Reduced intensity stem cell transplant on Day 0.

Drug: Tacrolimus

0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35.

Other Name: Prograf

Drug: Methotrexate

5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6.

Drug: G-CSF

5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.

Other Names:

Filgrastim
NeupogenTM

Procedure: Low Dose Donor T-Cells

Planned Donor Lymphocyte Infusion CD3+ cells: 3 * 106 CD3+ cells/kg between Day +56 and +64.

Experimental: High Dose Donor T-Cells

Fludarabine 40 mg/m2 by vein on Day -6 to -3. Melphalan 140 mg/m2 by vein on Day -2. Alemtuzumab 50 mg by vein on Day -1. Reduced intensity stem cell transplant on Day 0. High Dose Donor T-Cells Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64. Tacrolimus 0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35. Methotrexate 5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.

Drug: Fludarabine

40 mg/m2 by vein on Day -6 to -3.

Other Names:

Fludarabine Phosphate
Fludara

Drug: Melphalan

140 mg/m2 by vein on Day -2.

Other Name: Alkeran

Drug: Alemtuzumab

50 mg by vein on Day -1.

Other Names:

CAMPATH-1H
Campath

Procedure: Stem Cell Infusion

Reduced intensity stem cell transplant on Day 0.

Drug: Tacrolimus

0.015 mg/kg by vein as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml). Tacrolimus is changed to oral dosing when tolerated. Tapering should start on approximately Day +24 with intention to be completely off drug by approximately Day +35.

Other Name: Prograf

Drug: Methotrexate

5 mg/m2 dosed based on actual body surface area and administered intravenously on days +1, +3, +6.

Drug: G-CSF

5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.

Other Names:

Filgrastim
NeupogenTM

Procedure: High Dose Donor T-Cells

Planned Donor Lymphocyte Infusion CD3+ cells: 1 * 107 CD3+ cells/kg between Day +56 and +64.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age >/= 18 years and </= 65 years with one of the following: a. Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission. Patients in first remission should have intermediate or high cytogenetic risk factors or flt3 mutation. Patients with primary induction failure or relapse are eligible if they have <10% bone marrow blasts, and no circulating blasts. b. Myelodysplastic syndrome with intermediate or high risk IPSS score, or treatment related MDS. c. CML resistant to tyrosine kinase inhibitor treatment in a first or subsequent chronic phase, or in accelerated phase. d. CLL, Lymphoma or Hodgkin's disease which has failed to achieve remission or recurred following initial chemotherapy. Patients must have at least a PR to salvage therapy, or low bulk untreated relapse (<2 cm largest mass). e. Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy.
Patients must have one of the following donor types identified and willing to donate: a. Related donor, HLA-matched for HLA-A, -B, C and DR matched or, b. Matched Unrelated Donor (MUD), HLA-matched for HLA A, B, C and DRB1 using allele level typing.
Performance score of at least 80% by Karnofsky or performance score 0 to 2 (ECOG).
Estimated creatinine clearance >40 ml/min (based on serum creatinine)
Bilirubin <1.5 mg/dl except for Gilbert's disease.
ALT < 300 IU/ml d.
Left ventricular ejection fraction equal or greater than 40%.
Pulmonary function test (PFT) demonstrating a diffusion capacity (corrected for hemoglobin) of least 50% predicted.
Patient or patient's legal representative able to sign informed consent.

Exclusion Criteria:

Patients who have had prior autologous transplants or prior allogeneic transplants are not eligible.
Uncontrolled active infection.
Positive Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
Women of child bearing potential not willing to use an effective contraceptive measure while on study.
Subject has known sensitivity to any of the products that will be administered during the study.
Patients who are HIV seropositive.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01518153

Contacts

Contact: Richard E. Champlin, MD, BS

713-792-8750

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Richard E. Champlin, MD,BS

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01518153 History of Changes
Other Study ID Numbers:	2011-1104
Study First Received:	January 23, 2012
Last Updated:	April 30, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Blood and Marrow Transplantation
Lymphoma
Myeloma
Myeloproliferative Diseases
Leukemia
Myelodysplastic syndrome
MDS
Hodgkin disease
Multiple myeloma
Fludarabine
Fludarabine Phosphate
Fludara
Melphalan
Alkeran
Tacrolimus

Prograf
Methotrexate
G-CSF
Filgrastim
NeupogenTM
Donor Lymphocyte Infusion
DLI
Allogeneic Stem Cell Transplantation
Graft-vs-host disease
GvHD
T-lymphocytes
T-cells
Alemtuzumab
CAMPATH-1H
Campath

Additional relevant MeSH terms:

Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias

Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Melphalan
Fludarabine
Fludarabine monophosphate
Alemtuzumab
Methotrexate
Lenograstim
Tacrolimus
Campath 1G
Vidarabine
Myeloablative Agonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 18, 2013