Stem Cell Transplantation for Patients With Cancers of the Blood

NCT00467961 | Completed Phase 2 Results DMC

• 2 other identifiers: 07013607-H-0136
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body. Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.

Conditions

CML (Chronic Myelogenous Leukemia); CLL (Chronic Lymphocytic Leukemia); AML (Acute Myelogenous Leukemia); Acute Lymphocytic Leukemia; MDS (Myelodysplastic Syndrome)

Keywords

CML (Chronic Myelogenous Leukemia); CLL (Chronic Lymphocytic Leukemia); AML (Acute Myelogenous Leukemia); Leukemia; Chronic Lymphocytic Leukemia; CLL; Chronic Myelogenous Leukemia; CML; Acute Myelogenous Leukemia; AML; Acute B-Lymphoblastic Leukemia; ALL; Myelodysplastic Syndrome; MDS

Outcome Measures

Primary Outcomes (1)

• To Determine if Selective T Cell Depletion Using the Photodepletion Procedure Can Substantially Reduce the Rate of Severe Acute GVHD (Grade III/IV) After Matched Sibling Transplantation Followed by Low-dose or no Immunosuppression.

  Patients will receive a selectively photodepleted lymphocyte product which will be delivered together with the T cell depleted stem cell product on the day of transplantation. Subjects will receive a conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34-selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. To determine appropriate level of post transplant immunosuppression, a three sequential de-escalation stage design for timing of cyclosporine will be utilized. To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the number of severe acute GVHD (grade III/IV) after transplantation followed by low-dose or no immunosuppression.

  Day 90

Study Arms (1)

Miltenyi system transplant recipients

EXPERIMENTAL

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. Determine appropriate level of post transplant immunosuppression

Combination Product: Miltenyi system

Interventions

Miltenyi system COMBINATION_PRODUCT

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach.

Miltenyi system transplant recipients

Eligibility Criteria

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

You may qualify if:

• Recipient Criteria:
• Diagnosed with one of the following hematological conditions:
• Chronic myelogenous leukemia (CML): chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis; accelerated phase or blast transformation.
• Acute B-lymphoblastic leukemia (B-ALL): any of these categories: B-ALL in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia), all second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
• Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse.
• Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes.
• Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia.
• Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
• Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments.
• Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments.
• Ages 18-75 years inclusive.
• HLA identical (6/6) related donor.
• Ability to comprehend the investigational nature of the study and provide informed consent.
• Donor Criteria:
• Related HLA identical (6/6) with recipient.

You may not qualify if:

• Recipient Criteria (any of the following):
• Malignant cells expressing a T cell phenotype (in particular T-ALL and T cell NHL).
• DLCO less than 65 percent predicted.
• Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less than 30 percent (evaluated by MUGA).
• AST/SGOT greater than 10 times ULN (CTCAE grade IV v3.0).
• Bilirubin greater than 5 times ULN (CTCAE grade IV v3.0).
• Creatinine greater than 4.5 times ULN (CTCAE grade IV v 3.0).
• HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-1/II) are not excluded from participation).
• Positive pregnancy test for women of childbearing age.
• Prior allogeneic stem cell transplantation.
• Estimated probability of surviving less than three months.
• Major anticipated illness or organ failure incompatible with survival from transplant.
• Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
• Donor Criteria (any of the following):
• Pregnant or lactating.

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 (6)

• Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001 May 17;411(6835):385-9. doi: 10.1038/35077251.

  PMID: 11357147 BACKGROUND

• Amrolia PJ, Muccioli-Casadei G, Yvon E, Huls H, Sili U, Wieder ED, Bollard C, Michalek J, Ghetie V, Heslop HE, Molldrem JJ, Rooney CM, Schlinder J, Vitetta E, Brenner MK. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood. 2003 Sep 15;102(6):2292-9. doi: 10.1182/blood-2002-11-3516. Epub 2003 May 22.

  PMID: 12763937 BACKGROUND

• Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, Vitetta E, Schindler J, Chedeville G, Vilmer E, Fischer A, Cavazzana-Calvo M. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet. 2002 Jul 13;360(9327):130-7. doi: 10.1016/S0140-6736(02)09413-8.

  PMID: 12126823 BACKGROUND

• Mielke S, McIver ZA, Shenoy A, Fellowes V, Khuu H, Stroncek DF, Leitman SF, Childs R, Battiwalla M, Koklanaris E, Haggerty J, Savani BN, Rezvani K, Barrett AJ. Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies. Biol Blood Marrow Transplant. 2011 Dec;17(12):1855-61. doi: 10.1016/j.bbmt.2011.05.019. Epub 2011 May 31.

  PMID: 21684344 RESULT

• McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.

  PMID: 23524640 DERIVED

• Melenhorst JJ, Tian X, Xu D, Sandler NG, Scheinberg P, Biancotto A, Scheinberg P, McCoy JP Jr, Hensel NF, McIver Z, Douek DC, Barrett AJ. Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica. 2012 Jun;97(6):867-73. doi: 10.3324/haematol.2011.053363. Epub 2011 Dec 1.

  PMID: 22133778 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, B-Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory, with Excess of Blasts; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Minocher Battiwalla, MD
• Organization: NIH NHLBI

minoo.battiwalla@mail.nih.gov

301-827-0939

Study Officials

• Minocher M Battiwalla, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Model Details: Evaluation of selective depletion of alloreactive T cells to prevent graft vs host disease

Study Record Dates

• First Submitted: April 28, 2007
• First Posted: May 1, 2007
• Study Start: April 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: July 13, 2018
• Results First Posted: January 6, 2015

Record last verified: 2014-12

Locations

US (1)