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A Phase I Study of CYT107 (Recombinant Glycosylated Human IL-7) in Recipients of HLA Matched Ex Vivo T Cell Depleted Bone Marrow or Peripheral Blood Stem Cell Transplant

Phase 1
15 Years
Not Enrolling

Thank you

Trial Information

A Phase I Study of CYT107 (Recombinant Glycosylated Human IL-7) in Recipients of HLA Matched Ex Vivo T Cell Depleted Bone Marrow or Peripheral Blood Stem Cell Transplant

Rationale: Delayed and deficient reconstitution of T cells and their functions are a major
obstacle to the success of a hematopoietic stem cell transplant (HSCT). CYT-107 may have
potential clinical use after allogeneic HSCT to enhance lymphoid reconstitution which could
have a number of beneficial effects including decreased morbidity and mortality from
post-transplant infections. Our preliminary data with a previous generation IL-7, CYT 99
007, raise the possibility that IL-7 could have, in some cases, an anti-GVHD effect while
keeping the anti-tumor effect of the allograft intact.

Primary Objective:

- To determine the safety and a recommended dose of CYT107 (r-hIL-7) in recipients of
an HLA-matched related or unrelated ex vivo T-cell-depleted bone marrow (BM) or
peripheral blood stem cell (PBSC) transplant after initial engraftment and
hematopoietic reconstitution.

- If toxicities are encountered, to establish the maximum tolerated dose (MTD) and dose
limiting toxicities (DLT).

Secondary Objectives:

- To define the pharmacokinetics of escalating doses of CYT107 in recipients of
allogeneic transplants.

To achieve preliminary characterization:

- Of the effects of CYT107 treatment on engraftment and GVHD.

- Of the effects of CYT107 on the recovery of T, NK and B cell populations and their
functions in vitro.

- Of a tolerable biologically active range of doses for CYT107 in recipients of
allogeneic transplants.

- Whether and to what degree administration of CYT107 might influence the risk of
developing an EBV-lymphoproliferative disorder.

- Of the effects of CYT107 treatment on leukemia relapse.

Inclusion Criteria:

- 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.).

- 60 - 210 days post transplant.

- In remission at the time of initiation of CYT107.

- Documented engraftment with sustained neutrophil counts of at least 1000/mcl and
untransfused platelet counts > 20 000/mcl for 3 consecutive lab values (the last one
tested <10 days before initiation of treatment) on 3 different days prior to
treatment. Patients who have engrafted but require G-CSF for myelosuppressive
antibiotics or antiviral medications are eligible if they require G-CSF no more than
twice weekly and their ANC remains >1000/mcl.

- KPS > 60%.

- Adequate organ function:

- Cardiac: No evidence of change in cardiac function by history, exam and/or EKG

- Pulmonary: Absence of dyspnea or hypoxia (< 90% of saturation by pulse oxymetry
on room air).

- Hepatic: Bilirubin <= 1.5 X ULN, AST (SGOT) and /or ALT (SGPT) <= 2.5 X ULN.
PT/PTT < 1.5 X ULN.

- Renal: Calculated Creatinine clearance > 60 mL/min/1.73 m2. [Note: all
transplant patients had an ejection fraction of > 40% on their pre-transplant
echocardiogram and a DLCO > 50% of predicted (corrected for hemoglobin)]

Exclusion Criteria:

- No evidence or history of acute GVHD or of chronic GVHD.

- No recurrent leukemia post HCT.

- No active uncontrolled viral, bacterial or fungal infection.

- No documented HIV-1 or -2, HBV or HCV infection at any time before or after
transplant (a positive hepatitis B serology indicative of a previous immunization is
not an exclusion criteria).

- 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

- 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

- Fertile patients must use effective birth control. Not pregnant or nursing. Negative
pregnancy test within 2 weeks of study treatment.

- QTc prolongation (QTc > 470 ms) or prior history of significant arrhythmia or ECG

- No active drug or alcohol use or dependence that, in the opinion of the investigator,
would interfere with adherence to study requirements.

- Any past or current psychiatric illness that, in the opinion of the investigator,
would interfere with adherence to study requirements or the ability and willingness
to give written informed consent.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

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.

Safety Issue:


Principal Investigator

Marcel van den Brink, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

April 2011

Related Keywords:

  • AML
  • CML
  • MDS
  • 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



Memorial Sloan-Kettering Cancer Institute New York, New York  10065