Mini Allo Stem Cell Transplantation for the Treatment of Solid Tumors

NCT00997529 | Completed DMC

• 1 other identifier: E-00-0154-FB/2001-P-000092/8
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

A major focus of recent research has been the development of effective ways of sensitizing the patient's immune system to recognize the cancer as foreign. Allogeneic stem cell transplantation represents a novel way of potentially achieving this goal. There is recent evidence that non-myeloablative allogeneic stem cell transplantation provides effective therapy for patients with metastatic renal cell carcinoma. Based on the preliminary reports from other investigators treating patient with breast and ovarian cancer, the investigators of this study would propose treating an expanded cohort of patients with any metastatic solid tumor. The principal endpoints of the trial will include incidence of durable engraftment, quality of hematopoietic and immune reconstitution, extent of donor chimerism, incidence and severity of acute and chronic graft versus host disease (GVHD), and incidence of long-term disease free survival (DFS). The investigators will evaluate the tumor response of patients with stable or progressive disease post-transplant to donor lymphocyte infusions (DLI). The investigators will also study the effects of DLI on T-cell immunity in the recipients.

Conditions

Metastatic Solid Tumor

Keywords

Stem cell transplant; Non-myeloablative; Metastatic Solid Tumor; Donor Leukocyte Infusion

Outcome Measures

Primary Outcomes (2)

• To determine the percent 100-day survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic stem cell transplantation (SCT).

  100 days

• To determine the incidence of treatment-related toxicity and acute and chronic graft versus host disease.

  100 days

Secondary Outcomes (2)

• To determine the overall survival of patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT.

  2 years

• To evaluate the tumor response in patients with metastatic solid tumors undergoing non-myeloablative allogeneic SCT.

  2 years

Study Arms (1)

1

EXPERIMENTAL

Drug: nonmyeloablative stem cell transplant

Interventions

nonmyeloablative stem cell transplant DRUG

Conditioning includes cytoxan 60mg/kg/d on Days 6 \& 5, total dose 120mg/kg, Fludarabine 25mg/m2/d on days -5 to -1, total dose 125mg/m2. Patients with decreased cardiac or liver function pre-transplant will have their dose of cytoxan reduced by 25% - 45 mg/kg/d for 2 days or total dose of 90mg/kg. Patients will receive G-CSF (5ug/kg) to foster engraftment. PBSC progenitors will be mobilized from donor with G-CSF 5ug/kg 2x daily starting 4 days prior to stem cell collection until a target of 5-10 x106 CD34+ cells/kg is reached. Peripheral blood progenitors will be isolated from leukaphereses obtained on Days 5 \& 6 with additional collections dependent on cell yields. Peripheral blood from donors will be given to patients 1 day after cytoreduction \& immunosuppression. Immunosuppression will be tapered Day +60 if no signs of GVHD. Patients with residual non-regressing disease or mixed chimerism after day 100, who are off immunosuppression \& do not have signs of GVHD, will receive a DLI

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients:
• Candidates for this trial will be patients with metastatic solid tumors for whom no standard therapy exists or who have evidence of measurable disease that is clearly progressing following standard biologic therapy or chemotherapy for metastatic disease.
• Patients must have a healthy family member who is HLA-identical to the recipient and who is willing and able to receive a course of G-CSF and undergo 2- 4 daily leukaphereses.
• Each patient must be willing to participate as a research subject and must sign an informed consent form.
• Patients must be ambulatory with good performance status (ECOG 0 or 1; Karnofsky PS 100-80%).
• Patients must have adequate organ function as defined by:
• WBC \> 3000/mm3, plt \> 100,000/mm3, and hemoglobin \> 10gm/100ml
• Serum creatinine \< 1.8mg/dl or Cr clearance \> 60cc/min.
• Total bilirubin \< 1.5mg/dl
• No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias
• LVEF ≥40% by echocardiogram or MUGA scan (Patients whose LVEF is between 40% and 50% will have their cyclophosphamide dose reduced by 25% to 45 mg/kg/d for 2 days (total dose of 90 mg/kg).)
• FEV1 \> 2.0 liters or \> 75% of predicted for height and age.
• Patients must not be on systemic corticosteroids for intercurrent illness.
• Patients must be between 18 and 60 years of age. Patients over 60 will be accrued on an individual basis with approval of BMT service attendings.
• Women of childbearing potential must have a negative pregnancy test and not become pregnant while on treatment.

You may not qualify if:

• Patients:
• Patients with brain metastases, leptomeningeal disease or seizure. (NOTE: Patients with a history of brain metastases must be 6 months from definitive therapy (i.e. surgery or radiation) and have no evidence of disease or edema on brain CT scan or MRI.)
• Female patients who are pregnant or breast-feeding
• ECOG performance status \>1. (Karnofsky PS \<80%) (See Appendix 1.)
• Left ventricular ejection fraction of \< 40%.
• Active viral (e.g. chronic active hepatitis), bacterial or fungal infection.
• Patients seropositive for HIV, HTLV -1,
• Patients not providing informed consent.
• Patients with known hypersensitivity to E. coli-derived products.
• Donors:
• A positive HIV or HTLV-1 test or evidence of active/persistent viral hepatitis infection will exclude the donor from participation in this study. Donors who are HIV or HTLV-1 positive are ineligible because of the risk of transmission of virus during peripheral blood stem cell transplantation. Presence of any medical condition that would pose a serious health risk by undergoing peripheral blood stem cell harvest. Known hypersensitivity to E. coli-derived products.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Amgen: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David F McDermott, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: October 19, 2009
• Study Start: November 1, 2000
• Primary Completion: November 1, 2007
• Study Completion: June 1, 2010
• Last Updated: July 18, 2016

Record last verified: 2016-07

Locations

US (1)