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Report for Clinical Trial NCT01269424

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

06-benzylguanine (BG) and Temozolomide (TMZ) Therapy of Glioblastoma Multiforme (GBM) in Patients With MGMT Positive Tumors With Infusion of Autologous P140KMGMT+ Hematopoietic Progenitors to Protect Hematopoiesis

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving genetically modified peripheral blood stem cells during or after treatment may prevent side effects caused by chemotherapy. PURPOSE: This clinical trial studies O6-benzylguanine and temozolomide in combination with genetically modified peripheral blood stem cells in treating patients with newly diagnosed glioblastoma multiforme.

NCT01269424 Glioblastoma Multiforme
MeSH:Glioblastoma
HPO:Glioblastoma multiforme

7 Interventions

Name: MGMTP140K-encoding retroviral vector

Type: Biological
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: O6-benzylguanine

Type: Drug
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: temozolomide

Type: Drug
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: laboratory biomarker analysis

Type: Other
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: autologous hematopoietic stem cell transplantation

Type: Procedure
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: in vitro-treated peripheral blood stem cell transplantation

Type: Procedure
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3

Name: radiation therapy

Type: Radiation
Group Labels: 3

Cohort 1 Cohort 2 Cohort 3


Primary Outcomes

Description: Patients will be assessed for clinical symptoms and side-effects - CTCAE v 4.0 - from time of treatment until protocol is stopped due to toxicity, progression, patient choice, or patient election to enroll on new therapeutic option.

Measure: Feasibility and safety of infusing autologous P140K MGMT-transduced hematopoietic progenitors into patients with GBM

Time: up to 5 years

Secondary Outcomes

Description: Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors

Measure: Successful transduction rate

Time: up to 4 years

Description: To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ

Measure: To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ

Time: up to 4 years

Description: Progression-free survival defined as the time interval between the date of initial histological diagnosis and the date of disease progression or death, whichever comes first

Measure: Progression-free

Time: up to 5 years

Description: New tumor or increased tumor size on T1WI + Gd of > 25% as measured by the sum of two perpendicular diameters compared to the smallest measurements ever recorded for the same lesion by the same technique.

Measure: Number of patients with radiological progression

Time: up to 5 years

Description: From the date of enrollment to death, last contact or last tumor assessment before further anti-tumor therapy, assessed up to 5 years.

Measure: Overall Survival

Time: up to 5 years

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 P140K

Feasibility and safety of infusing autologous P140K MGMT-transduced hematopoietic progenitors into patients with GBM. --- P140K ---

Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors. --- P140K ---

Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors. --- P140K --- --- P140K ---

To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ. --- P140K ---

- Prior diagnosis of malignant disease within a three year period with the exception of surgically cured basal cell carcinoma or carcinoma in situ of the cervix - Mental incapacity or psychiatric illness preventing informed consent Glioblastoma Multiforme Glioblastoma OBJECTIVES: Primary - To evaluate the feasibility of introducing and expressing P140K MGMT cDNA from a lentiviral-based provirus in autologous hematopoietic stem cells harvested from Glioblastoma multiforme (GBM) patients. --- P140K ---

- To assess the safety associated with infusion of autologous hematopoietic stem cells transduced ex vivo with a lentiviral vector expressing P140K MGMT in patients with GBM. --- P140K ---

Secondary - To determine whether any patients who receive P140K MGMT-transduced CD34 cells tolerate O6-benzylguanine (BG) and dose-escalated temozolomide (TMZ) without myelosuppression. --- P140K ---

- To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors. --- P140K ---

- To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors. --- P140K --- --- P140K ---

- To evaluate the feasibility of in vivo enrichment of P140K-expressing hematopoietic cells by repeated treatments of BG and TMZ at doses that appear therapeutic for GBM. - To evaluate the efficacy of various types of chemotherapy with or without radiotherapy on conditioning the patient's bone marrow to host the transduced autologous hematopoetic stem cells. --- P140K ---

- Cohort 1 (LV P140K MGMT gene transfer after concurrent chemoradiotherapy): Patients receive radiotherapy (60cGy in 30 2cGy daily doses) and TMZ 75mg/m2 /daily for 6 weeks, cell infusion at week 7 (T0) followed by BG 120 mg/m2 intravenous infusion over 1h and TMZ 50 mg/m2/day x 5 days, every 28 days (starting on T+28) for 6 cycles. --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K --- --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K --- --- P140K --- --- P140K ---



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