Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2013
• Main ID: NCT01403415
• Date of registration: 21/07/2011
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
• Scientific title: A Phase 1 Study of Temsirolimus (CCI-779, IND# 61010) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma
• Date of first enrolment: September 2011
• Target sample size: 60
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01403415
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Canada, United States

Contacts

• Name: Susan Rheingold
• Affiliation: COG Phase I Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis:

- Patients must have 2nd or greater relapse of pre-B ALL, T-cell ALL,
lymphoblastic lymphoma, or peripheral T-cell lymphoma; patients may not have
refractory disease

- Patients with ALL, lymphoblastic lymphoma or peripheral T-cell lymphoma
refractory to first relapse therapy are eligible for enrollment

- Patients with leukemia must have had histologic verification of the malignancy
at the most recent relapse, including immunophenotyping to confirm diagnosis

- Disease Status:

- Leukemia: Patients with leukemia must have an M3 marrow with or without
extramedullary site of relapse OR an M2 bone marrow with an extramedullary site
of relapse; patients with CNS 3 status are not eligible for enrollment

- Lymphoma: Patients with non-Hodgkin lymphoma must have either measurable or
evaluable disease

- Patient's current disease state must be one for which there is no known curative
therapy or therapy proven to prolong survival with an acceptable quality of life

- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age; patients who are unable to walk because of paralysis, but who are up in
a wheelchair, will be considered ambulatory for the purpose of assessing the
performance score

- Prior Therapy:

- Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer chemotherapy, defined as resolution of all such toxicities to =<
Grade 2 or per the inclusion/exclusion criteria

- Myelosuppressive chemotherapy:

- Patients with leukemia or lymphoma who relapse while receiving standard
maintenance chemotherapy with steroid, vincristine pulses and oral
outpatient chemotherapy will not be required to have a waiting period
before enrollment onto this study

- Patients who relapse while they are not receiving standard maintenance
therapy, must have fully recovered from all acute toxic effects of prior
therapy; at least 14 days must have elapsed after the completion of
cytotoxic therapy, with the exception of hydroxyurea

- Note: Cytoreduction with hydroxyurea in patients can be initiated and
continued for up to 24 hours prior to the start of protocol therapy

- Hematopoietic growth factors: At least 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which
adverse events are known to occur; the duration of this interval must be
discussed with the study chair

- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a
biologic agent. For agents that have known adverse events occurring beyond 7
days after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must be
discussed with the study chair

- Immunotherapy: At least 42 days after the completion of any type of
immunotherapy, e.g. tumor vaccines

- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose
of a monoclonal antibody with the exception of blinatumomab; patients must have
been off blinatumomab infusion for at least 7 days and all drug-related toxicity
must have resolved to Grade 1 or lower as outline in the inclusion and exclusion
criteria

- XRT: At least 14 days after local palliative XRT (small port); At least 84 days
must have elapsed if prior TBI, craniospinal XRT or if >= 50% radiation of
pelvis; At least 42 days must have elapsed if other substantial BM radiation

- Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84
days must have elapsed after transplant or stem cell infusion

- Study specific limitations on prior therapy: Patient may not have received prior
therapy with an mTOR inhibitor

- Platelet count >= 20,000/mm^3 (may receive platelet transfusions) to initiate therapy

- Patients must not be known to be refractory to red cell or platelet transfusion

- Creatinine clearance or radioisotope GFR >= 70ml/min/1.73 m^2

- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age

- SGPT (ALT) =< 225 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

- GGT =< ULN for age

- Serum albumin >= 2 g/dL

- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
gated radionuclide study

- Pulse oximetry > 94% on room air

- Baseline chest x-ray; patients with active infectious disease or pneumonitis are not
eligible

- Serum triglyceride level =< 300 mg/dL and serum cholesterol level =< 300 mg/dL

- Random or fasting blood glucose within the upper normal limits for age; iIf the
initial blood glucose is a random sample that is above the upper normal limits, then
a follow-up fasting blood glucose can be obtained and must be within the upper normal
limits for age

- All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines

- Patients who are currently receiving other anticancer agents are not eligible (except
patients receiving hydroxyurea, which may be continued until 24 hours prior to start
of protocol therapy)

Exclusion Criteria:

- Pregnant or breast-feeding women will not be entered on this study

- Patients receiving stable or decreasing doses of corticosteroids for =< 7 days prior
to enrollment, or who are receiving increasing doses of corticosteroids, are not
eligible for enrollment; the exception to this is pulsed steroids used for
maintenance chemotherapy

- Patients who are currently receiving another investigational drug are not eligible

- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial

- Patients who cannot receive asparginase are not permitted on trial; substitution with
Asparaginase Erwinia Chrysanthemi is acceptable

- Cumulative prior anthracy


Age minimum: 1 Year
Age maximum: 21 Years
Gender: Both

Health Condition(s) or Problem(s) studied

B-cell Childhood Acute Lymphoblastic Leukemia

Peripheral T-cell Lymphoma

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent Childhood Lymphoblastic Lymphoma

T-cell Childhood Acute Lymphoblastic Leukemia

Intervention(s)

Drug: dexamethasone

Drug: methotrexate

Drug: mitoxantrone hydrochloride

Drug: pegaspargase

Drug: temsirolimus

Drug: vincristine sulfate

Other: laboratory biomarker analysis

Other: pharmacological study

Primary Outcome(s)

Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0 [Time Frame: Up to 30 days post-treatment]

MTD and/or recommended phase II dose of temsirolimus in combination with intensive re-induction chemotherapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [Time Frame: Up to day 36]

Secondary Outcome(s)

Comparison between MRD levels present at the end of induction with historical control in patients with bone marrow involvement of disease [Time Frame: Up to 30 days post-treatment]

CR rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [Time Frame: Up to 30 days post-treatment]

In vitro and in vivo pharmacodynamics of temsirolimus [Time Frame: Up to 30 days post-treatment]

Secondary ID(s)

ADVL1114

CDR0000703889

COG_ADVL1114

NCI-2011-02679

U01CA097452

Source(s) of Monetary Support

Please refer to primary and secondary sponsors