Ultra-Low Dose IL-2 Therapy as GVHD Prophylaxis in Haploidentical Allogeneic Stem Cell Transplantation

NCT02226861 | Completed Phase 1

• 2 other identifiers: 14018014-H-0180
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Stem cell transplantation from a partially matched donor can lead to graft-versus-host disease (GVHD). Researchers want to learn how to improve these transplantations. Objective: \- To see if very low doses of Interleukin-2 after a partially matched transplantation prevent GVHD. Eligibility:

• Recipients: age 18 65, with certain bone marrow or lymphatic system diseases and an available family member with partial tissue match.
• Donors: age 18 80. Design:
• Recipients will be screened with medical history, physical exam, and many tests including blood and tissue tying.
• Donors will be screened with medical history, physical exam, blood tests and tissue typing.
• Recipients will stay in the hospital 3 6 weeks.
• All participants will have apheresis. Blood is drawn from one arm, run through a machine that collects white blood cells, then returned into the other arm.
• Recipients will have:
• Intravenous (IV) line placed under the skin and into a neck vein, to stay throughout transplant and recovery. They may also have a catheter inserted for collecting immune cells.
• Bone marrow sample taken by needle. They will have 3 more after transplant.
• Donors will have:
• Filgrastim injected once daily for 5 6 days.
• Stem and immune cells collected by another apheresis.
• Recipients will get:
• Eight 30-minute doses of radiation, sitting at a machine.
• Donor immune cells by IV, 6 days before the transplant day.
• Chemotherapy drugs by IV. \<TAB\>\<TAB\>- Donor stem cells by IV on transplant day.
• After transplant, recipients will give self-injections of very low doses of Interleukin-2 once daily for about 12 weeks.
• Before and after transplant, recipients will get medicine to suppress the immune system and antibiotics to prevent infections
• Recipients must stay near NIH for 3 6 months after transplant.
• All recipients and donors will have 3 years of follow-up.

Conditions

Acute Lymphoblastic Leukemia (ALL); Acute Myelogenous Leukemia (AML); Chronic Lymphocytic Leukemia (CLL); Chronic Myelogenous Leukemia (CML); MDS

Keywords

Acute Lymphoblastic Leukemia (ALL); MDS; Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Acute Myelogenous Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Safety of ULD IL-2 as GVHD proph

  The primary endpoint to this study is to evaluate the safety of ULD IL-2 as GVHD prophylaxis in haploidentical transplantation.

  4 months

Study Arms (1)

1

EXPERIMENTAL

Subjects will receive CD34-selected stem cells followed by fixed dose ULG IL-2 (100,000 IU/m2) given subcutaneously for 12 weeks+Sirolimus until Day +60

Device: CliniMACS CD34 selection system; Biological: ULD IL-2

Interventions

CliniMACS CD34 selection system DEVICE

Stem cells will be selected with the CliniMACS system before transplant.

1

ULD IL-2 BIOLOGICAL

sterile, white to off-white, preservative-free, lyophilized powder suitable for IV infusion upon reconstitution and dilution

1

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 18-70 years inclusive
• Haploidentical donor available
• Any one of the following hematologic conditions meeting a standard indication for allogeneic stem cell transplant:
• Chronic myelogenous leukemia (CML): Subjects under the age of 21 in chronic phase OR subjects ages 18-65 in chronic phase who have failed treatment with imatinib or have intolerance to imatinib OR Subjects ages 18-65 in accelerated phase or blast transformation. OR
• Acute lymphoblastic leukemia (ALL): any of these categories: Adult ALL including standard risk. All second or subsequent remissions, primary induction failure, partially responding or untreated relapse. OR
• Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), c-kit unmutated AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse. OR
• Myelodysplasticsyndromes(MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with ANC\<500/ (Micro)L, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes. OR
• Myeloproliferative disorders including atypical (Ph-negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia either in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia. OR
• Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments. OR
• Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments. OR
• Hodgkin's Lymphoma relapsing following an autologous transplant. OR
• Other rare hematologic malignancies for which hematopoietic stem cell transplantation has been performed and offers a durable remission or as the only option with a potential for cure.
• Chemotherapy-resistant multisystem Langerhans cell histiocytosis (MSLCH) especially involving organs like the bone marrow, liver, spleen, and lungs
• Aggressive systemic mastocytosis, and mast cell leukemia (MCL) in first CR (CR1)
• Hypereosinophilic syndrome who have failed imatinib therapy or FIP1L1-PDGFRa-negative patients who develop end-organ dysfunction

You may not qualify if:

• HLA identical (6/6) related or (8/8 allele level matched) unrelated donor available and readily accessible at time of transplantation evaluation
• 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 making informed consent impossible.
• Positive pregnancy test for women of childbearing age
• Contraindication to receive IL-2 including:
• Hypersensitivity to IL-2
• Sustained ventricular tachycardia (\>5 beats)
• Cardiac arrhythmias not controlled or unresponsive to management
• Chest pain with ECG changes, consistent with angina or myocardial infarction
• Cardiac tamponade
• Intubation for \>72 hours
• Renal failure requiring dialysis \>72 hours
• Coma or toxic psychosis lasting \> 48 hours
• Repetitive or difficult to control seizures
• Active bowel ischemia or perforation

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 (3)

• Grosso D, Carabasi M, Filicko-O'Hara J, Kasner M, Wagner JL, Colombe B, Cornett Farley P, O'Hara W, Flomenberg P, Werner-Wasik M, Brunner J, Mookerjee B, Hyslop T, Weiss M, Flomenberg N. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011 Oct 27;118(17):4732-9. doi: 10.1182/blood-2011-07-365338. Epub 2011 Aug 25.

  PMID: 21868572 BACKGROUND

• Barrett J, Gluckman E, Handgretinger R, Madrigal A. Point-counterpoint: haploidentical family donors versus cord blood transplantation. Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S89-93. doi: 10.1016/j.bbmt.2010.10.024. No abstract available.

  PMID: 21195317 BACKGROUND

• Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program. 2012;2012:230-6. doi: 10.1182/asheducation-2012.1.230.

  PMID: 23233586 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

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

Study Officials

• Sawa Ito, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 27, 2014
• Study Start: August 26, 2014
• Primary Completion: May 23, 2018
• Study Completion: June 27, 2018
• Last Updated: July 5, 2018

Record last verified: 2018-06-27

Locations

US (1)