Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS

NCT00025662 | Completed Phase 2 Results DMC

• 2 other identifiers: 01016201-H-0162
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and effectiveness of stem cell transplantation in which the donors T lymphocytes have undergone "selective depletion." Certain patients with cancers of the blood undergo transplantation of donated stem cells to generate new and normally functioning bone marrow. In addition to producing the new bone marrow, the donor's T-lymphocytes also fight any tumor cells that might have remained in the body. This attack on tumor cells is called a "graft-versus-leukemia" (GVL) effect. However, another type of T-lymphocyte from the donor may cause what is called "graft-versus-host-disease" (GVHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to reject them. Selective depletion is a technique that was developed to remove the T-lymphocytes that cause harmful GVHD, while keeping those that produce the desirable GVL effect.

Conditions

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

Keywords

Peripheral Blood Stem Cell; Melphalan; Fludarabine; Donor Apheresis; Non-Myeloablative; MDS; Chronic Myeloid Leukemia; CML; Chronic Lymphocytic Leukemia; CLL; Lymphoma; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Mantle Cell Lymphoma; Acute Myelogenous Leukemia (AML); Chronic Myeloid Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Myelodysplasia (MDS); Acute Lymphoblastic Leukemia (ALL); Bone Marrow Transplant

Outcome Measures

Primary Outcomes (1)

• Treatment-related Mortality

  Nonrelapse mortality in the first 100 days of transplant expressed as a percentage of the total subjects. This is different from outcome measure 3 (Cumulative Nonrelapse Mortality), which is cumulative non relapse mortality till December 2011.

  100 days after stem cell infusion

Secondary Outcomes (2)

• Overall Survival

  Dec 2011.

• Cumulative Non Relapse Mortality

  Dec 2011.

Other Outcomes (2)

• Acute GVHD (Any Grade) Using the CIBMTR Grading System.

  100 days from transplant

• Acute GVHD (Grade 3 or 4) Using the CIBMTR Grading System.

  100 days from transplant

Study Arms (1)

RFT5-SMPT-dgA Isolex system

EXPERIMENTAL

RFT5-SMPT-dgA, a specific anti-interleukin-2 receptor immunotoxin used in allogeneic stem cell transplantation (SCT) in older patients with hematologic malignancies using a graft manipulation process

Drug: RFT5-SMPT-dgA; Drug: Isolex system

Interventions

RFT5-SMPT-dgA DRUG

A specific anti-interleukin-2 receptor immunotoxin

Also known as: anti-interleukin-2 receptor immunotoxin

RFT5-SMPT-dgA Isolex system

Isolex system DRUG

CD34 selection/ T cell depletion used this system

Also known as: Nexell Isolex system

RFT5-SMPT-dgA Isolex system

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 50-75 years
• Relapsed CML in chronic or accelerated phase after therapy with STI-571 (Gleevec)
• Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission. Exceptions: T cell ALL
• Acute myelogenous leukemia (AML): AML in first complete or partial remission including AML secondary to chemotherapy or prior hematological disease such as myelodysplastic syndrome, and myeloproliferative disorder.
• Myelodysplastic syndromes: (1) refractory anemia with excess of blasts (RAEB), (2) refractory anemia with excess blasts in transformation (RAEBT), (3) MDS with poor risk cytogenetics defined by a complex karyotype (greater than or equal to three anomalies) or chromosome 7 abnormalities, (4) secondary MDS after prior cytotoxic or radiation therapy, or (5) chronic myelomonocytic leukemia (CMML)
• Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, refractory to nucleoside analog therapy, with either progressive bulky disease or anemia (less than 10 g/dl) or thrombocytopenia (less than 100,000/microliter) not due to recent chemotherapy
• Mantle cell lymphoma
• Relapsed intermediate- or high-grade non-Hodgkin's lymphoma: (1) post autologous marrow or PBSC transplant, or (2) chemorefractory relapse. Exceptions: T cell NHL
• Relapse Hodgkin's disease: (1) post autologous marrow or PBSC transplant, or (2) chemorefractory relapse
• Low-grade follicular or small lymphocytic lymphoma: (1) relapsed following conventional chemotherapy, (2) relapsed following autologous marrow or PBSC transplant, or (3) chemoresistant disease
• Life expectancy greater than 3 months
• Ability to comprehend the investigational nature of the study and provide informed consent
• Availability of an HLA-identical family donor, 18 to 75 years old
• DONOR
• HLA identical family donor, 18 to 75 years old

You may not qualify if:

• RECIPIENT
• Pregnant or lactating
• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more
• Major anticipated illness or organ failure incompatible with survival from PBSC transplant
• Diffusion Capacity fir carbon monoxide (DLCO) less than 60% predicted
• Left ventricular ejection fraction less than 40%, or any angina.
• Absolute lymphocyte count less than 300/mm(3)
• Serum creatinine greater than 2.5 mg/dl
• Serum bilirubin greater than 4 mg/dl, transaminases greater than 5x upper limit of normal
• HIV positive
• Other malignant diseases liable to relapse or progress within 2 years
• DONOR
• Pregnant or lactating
• HIV positive. Donors who are positive for Hepatitis B Virus, Hepatitis C Virus or human t-cell lymphoma virus (HTLV) will be used at the discretion of the investigator and with appropriate consent of the recipient
• Donor unfit to receive G-CSF and undergo apheresis (uncontrolled hypertension, history of heart failure or unstable angina, platelet count less than 90,000/cu mm)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Barrett J, Solomon S. The transition from bench to bedside: lessons learned in the creation of a new T-cell product for the clinic. Cytotherapy. 2004;6(6):593-5. doi: 10.1080/14653240410011936.

  PMID: 15764025 BACKGROUND

• Solomon SR, Tran T, Carter CS, Donnelly S, Hensel N, Schindler J, Bahceci E, Ghetie V, Michalek J, Mavroudis D, Read EJ, Vitetta ES, Barrett AJ. Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation. Cytotherapy. 2002;4(5):395-406. doi: 10.1080/146532402320775982.

  PMID: 12473206 BACKGROUND

• Mielke S, Solomon SR, Barrett AJ. Selective depletion strategies in allogeneic stem cell transplantation. Cytotherapy. 2005;7(2):109-15. doi: 10.1080/14653240510018172.

  PMID: 16040390 BACKGROUND

• Solomon SR, Mielke S, Savani BN, Montero A, Wisch L, Childs R, Hensel N, Schindler J, Ghetie V, Leitman SF, Mai T, Carter CS, Kurlander R, Read EJ, Vitetta ES, Barrett AJ. Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood. 2005 Aug 1;106(3):1123-9. doi: 10.1182/blood-2005-01-0393. Epub 2005 Apr 7.

  PMID: 15817673 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphoid; Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

RFT5-SMPT-dgA immunotoxin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: A. John Barrett
• Organization: NHLBI

barrettjj@mail.nih.gov

301-402-4170

Study Officials

• A. J Barrett, MD

  NHLBI, NIH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2001
• First Posted: January 27, 2003
• Study Start: May 1, 2001
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: October 28, 2016
• Results First Posted: January 13, 2012

Record last verified: 2016-09

Locations

US (1)