Planned Donor Lymphocyte Infusion (DLI) After Allogeneic Stem Cell Transplantation (SCT)

NCT01518153 | Terminated Phase 2 Results

• 2 other identifiers: 2011-1104NCI-2012-00131
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Lymphoma; Myeloma; Myeloproliferative Diseases

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Success Rate

  Success rate defined as alive, engrafted without grade 3 or 4 GvHD or relapse at day 100 post allogeneic stem cell transplantation followed by donor lymphocyte infusion (DLI).

  100 days

Secondary Outcomes (1)

• Overall Survival (OS)

  Every 3 months until day of death

Study Arms (2)

Low Dose Donor T-Cells

EXPERIMENTAL

Fludarabine 40 mg/m\^2 by vein on Day -6 to -3. Melphalan 140 mg/m\^2 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; Drug: Melphalan; Drug: Alemtuzumab; Procedure: Stem Cell Infusion; Drug: Tacrolimus; Drug: Methotrexate; Drug: G-CSF; Procedure: Low Dose Donor T-Cells

High Dose Donor T-Cells

EXPERIMENTAL

Fludarabine 40 mg/m\^2 by vein on Day -6 to -3. Melphalan 140 mg/m\^2 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; Drug: Melphalan; Drug: Alemtuzumab; Procedure: Stem Cell Infusion; Drug: Tacrolimus; Drug: Methotrexate; Drug: G-CSF; Procedure: High Dose Donor T-Cells

Interventions

Fludarabine DRUG

40 mg/m\^2 by vein on Day -6 to -3.

Also known as: Fludarabine Phosphate, Fludara

High Dose Donor T-Cells; Low Dose Donor T-Cells

Melphalan DRUG

140 mg/m\^2 by vein on Day -2.

Also known as: Alkeran

High Dose Donor T-Cells; Low Dose Donor T-Cells

Alemtuzumab DRUG

50 mg by vein on Day -1.

Also known as: CAMPATH-1H, Campath

High Dose Donor T-Cells; Low Dose Donor T-Cells

Stem Cell Infusion PROCEDURE

Reduced intensity stem cell transplant on Day 0.

High Dose Donor T-Cells; Low Dose Donor T-Cells

Tacrolimus DRUG

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.

Also known as: Prograf

High Dose Donor T-Cells; Low Dose Donor T-Cells

Methotrexate DRUG

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

High Dose Donor T-Cells; Low Dose Donor T-Cells

G-CSF DRUG

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

Also known as: Filgrastim, NeupogenTM

High Dose Donor T-Cells; Low Dose Donor T-Cells

Low Dose Donor T-Cells PROCEDURE

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

Low Dose Donor T-Cells

High Dose Donor T-Cells PROCEDURE

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

High Dose Donor T-Cells

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Lymphoma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Hodgkin Disease; Multiple Myeloma; Graft vs Host Disease

Interventions

fludarabine; fludarabine phosphate; Melphalan; Alemtuzumab; Tacrolimus; Methotrexate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Richard E. Champlin, MD/Chair, Stem Cell Transplantation
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-8750

Study Officials

• Richard E. Champlin, MD,BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 23, 2012
• First Posted: January 25, 2012
• Study Start: February 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 17, 2016
• Results First Posted: March 17, 2016

Record last verified: 2016-02

Locations

US (1)