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.
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.
- 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
- If toxicities are encountered, to establish the maximum tolerated dose (MTD) and dose
limiting toxicities (DLT).
- To define the pharmacokinetics of escalating doses of CYT107 in recipients of
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
- 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.
- 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)]
- 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
- 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
- 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
- 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.