Safety Study of IL-7 in Recipients of a Hemopoietic Stem Cell Transplant Peripheral Blood Stem Cell Transplant

NCT00684008 | Completed Phase 1 DMC

• 2 other identifiers: CLI-107-08MSKCC IRB #07-127
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I inter-patient dose escalation open labeled study assessing multiple doses of CYT107 in patients of at least 15 years of age, who are recipients of HLA matched ex vivo T cell depleted bone marrow or peripheral blood stem transplants. The dose escalation design is aimed at establishing the absence of significant toxicity and to define a biologically active dose in this patient population. At each dose level, eligible patients will receive 3 doses of CYT107 injected subcutaneously (under the skin of the arm, legs, or stomach) once a week for 3 weeks. Groups of three patients will be entered at each dose level of CYT107. Three dose levels are planned: 10 mcg/kg/week, 20 mcg/kg/week and 30 mcg/kg/week. Three patients must complete day 42 of the study at a dose level without a dose limiting toxicity (DLT) before there is escalation to the next dose level.

Conditions

AML; CML; MDS

Keywords

interleukin-7; immune based therapies; graft vs host disease; immune reconstitution; infection; lymphopenia; hematopoetic stem cell transplantation; bone marrow transplantation; peripheral blood stem cell transplant; immunosuppression

Outcome Measures

Primary Outcomes (1)

• Toxicity of CYT107 in post-transplant patients with AML, CML and MDS using the NCI Common Toxicity Criteria version 3.0 with the BMT specific adverse event grading system.

  Visits: 2 week screening period; treatment visits on days 0, 7, and 14; non-treatment visits on Days 1, 21, 28, 42, 56, and 77.

Secondary Outcomes (1)

• Pharmacokinetics and Pharmacodynamics

  Study days 0, 1, 7, 14, 21, 28, 42, and 77.

Study Arms (1)

I

EXPERIMENTAL

Single arm dose escalation study. Three successive cohorts of 3 patients each. Doses to be evaluated: 10, 20, and 30 mcg/kg/dose for 3 consecutive doses. CYT107 is a recombinant protein belonging to the class of growth factors known as cytokines. CYT107 is a heavily glycosylated and sialylated form of recombinant human Interleukin-7. CYT107 is supplied as a sterile colorless liquid at a concentration of 4 mg/ml.

Drug: CYT107 - Recombinant glycosylated human interleukin 7.; Drug: rhIL-7 (CYT107)

Interventions

CYT107 - Recombinant glycosylated human interleukin 7. DRUG

Patients will be treated with CYT107 60 to 210 days post transplantation, in 3 successive cohorts of 3 patients. Escalating doses of CYT107 will be given to successive cohorts. Patients will receive 1 dose of CYT107 by the subcutaneous route, once a week for 3 weeks. Dose level 1: 10 mcg/kg/dose for 3 doses; Dose level II: 20 mcg/kg/dose for 3 doses; Dose level III: 30 mcg/kg/dose for 3 doses. Only 1 treatment course for this initial study.

Also known as: rhIL-7

I

rhIL-7 (CYT107) DRUG

10, 20, or 30 mcg/kg once a week for 3 consecutive weeks via the subcutaneous route.

Also known as: interleukin-7

I

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to read consent form and give informed consent.
• At least 15 years old.
• Histologically confirmed non-lymphoid hematological malignancy.
• Recipient of T cell depleted bone marrow (BM) or peripheral blood stem cell (PBSC) transplant from a 6/6 HLA (A, B, DR by intermediate resolution) identical related or unrelated donor after myeloablative conditioning.
• Received TCD HCT containing \< 1x105 CD3+ T cells/kg of recipient.
• Patient included in at least one of the following categories:
• AML in 2nd or greater complete remission.
• High-risk AML (high-risk cytogenetics, undifferentiated leukemia, secondary AML, antecedent MDS) in 1st remission.
• CML in 2nd or greater chronic phase, 2nd or greater accelerated phase.
• MDS intermediate or high risk by IPSS criteria.
• History of opportunistic infection (CMV viremia requiring anti-viral therapy, PCP pneumonia, mycobacterial infection, herpes zoster, viral respiratory infection (influenza, RSV, para-influenza), etc.
• CD4+ T cell count \< 100 at 6 months post-transplant.
• At high risk for opportunistic infection (e.g., history of treated invasive fungal infection prior to the transplantation, positive CMV serology in patient, or positive toxoplasmosis serology in donor and patient, etc.).
• days post transplant.
• In remission at the time of initiation of CYT107.

You may not qualify if:

• No evidence or history of acute GVHD or of chronic GVHD.
• No recurrent leukemia post HCT.
• No active uncontrolled viral, bacterial or fungal infection.
• Not be receiving systemic corticosteroid, anti-mitotic agent or other immunosuppressive treatment.
• Not receiving Growth Hormone or gonadotropin agonists/ antagonists.
• Not receiving any cytokine support other than G-CSF post-HCT.
• Not receiving concurrent treatment with another investigational drug and/or biological agent.
• Not receiving anticoagulant therapy.
• No uncontrolled hypertension.
• No history of lymphoid malignancy (e.g. Hodgkin disease, non Hodgkin lymphoma, Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia) or acute biphenotypic leukemia.
• No peripheral lymphadenopathy (any lymph node \> 1 cm).
• No history of EBV associated lymphoproliferation.
• No EBV viremia equal to or greater than 500 copies EBV DNA/mL of blood by quantitative PCR.
• No history of autoimmune disease nor a HCT donor with a history of an autoimmune disease.
• Fertile patients must use effective birth control. Not pregnant or nursing. Negative pregnancy test within 2 weeks of study treatment.

Sponsors & Collaborators

• Cytheris, Inc.: lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Institute

New York, New York, 10065, United States

Location

Related Publications (3)

• Alpdogan O, Muriglan SJ, Eng JM, Willis LM, Greenberg AS, Kappel BJ, van den Brink MR. IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J Clin Invest. 2003 Oct;112(7):1095-107. doi: 10.1172/JCI17865.

  PMID: 14523046 BACKGROUND

• Rosenberg SA, Sportes C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006 May-Jun;29(3):313-9. doi: 10.1097/01.cji.0000210386.55951.c2.

  PMID: 16699374 BACKGROUND

• Perales MA, Goldberg JD, Yuan J, Koehne G, Lechner L, Papadopoulos EB, Young JW, Jakubowski AA, Zaidi B, Gallardo H, Liu C, Rasalan T, Wolchok JD, Croughs T, Morre M, Devlin SM, van den Brink MR. Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation. Blood. 2012 Dec 6;120(24):4882-91. doi: 10.1182/blood-2012-06-437236. Epub 2012 Sep 25.

  PMID: 23012326 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Infections; Lymphopenia

Interventions

efineptakin alfa; Interleukin-7

Condition Hierarchy (Ancestors)

Immune System Diseases; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Marcel van den Brink, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 21, 2008
• First Posted: May 26, 2008
• Study Start: March 1, 2008
• Study Completion: April 1, 2011
• Last Updated: July 26, 2012

Record last verified: 2012-07

Locations

US (1)