Chemotherapy and Peripheral Stem Cell Transplantation Followed by Immunotherapy in Treating Patients With Chronic Myelogenous Leukemia

Leukemia Clinical Trial

Official title:

Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003727
• Other study ID #: CDR0000066839
• Secondary ID: MSGCC-9851MSGCC-
• Status: Completed
• Phase: Phase 2
• Start date: March 1999
• Est. completion date: February 2008

Study information

• Verified date: October 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with a peripheral stem cell transplant and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: This phase II trial is studying giving chemotherapy together with a peripheral stem cell transplant followed by immunotherapy to see how well it works in treating patients with chronic phase chronic myelogenous leukemia.

Description:

OBJECTIVES:

• Determine the feasibility of ex vivo expansion and reinfusion of autologous CD4+ T cells after interferon therapy or high-dose chemotherapy with CD34-selected autologous peripheral blood stem cell rescue in patients with chronic phase chronic myelogenous leukemia (CML).

• Determine the frequency of hematologic, cytogenetic, and molecular remissions of CML following infusion of ex vivo expanded T cells.

OUTLINE: Patients undergo mononuclear cell leukapheresis to obtain T cells for ex-vivo expansion, preferably before they receive interferon alfa subcutaneously (SC) daily on a therapeutic trial.

At least 1 month after interferon is stopped, mobilization chemotherapy is administered. Patients receive cyclophosphamide IV over 12 hours on day 0, etoposide IV over 2 hours on day 1, sargramostim (GM-CSF) SC on days 3 and 4, and filgrastim (G-CSF) SC beginning on day 5. Peripheral blood stem cells (PBSC) are collected by leukapheresis when blood cell counts have recovered.

Approximately 2-3 weeks later, high-dose chemotherapy begins. Patients receive gemcitabine IV over 100 minutes on day -5, carmustine IV over 2 hours on day -2, followed 6 hours later by gemcitabine IV again, and melphalan IV over 20 minutes on day -1. CD34 selected PBSCs are infused on day 0, at least 18 hours after melphalan administration. Patients receive GM-CSF SC beginning on day 1 and continuing until blood cell counts recover.

Patients then receive ex vivo expanded autologous T cells on day 14 after autotransplantation. Interferon alfa is administered three times a week starting about 3 months after transplantation.

Patients who only receive expanded T cells, without high-dose chemotherapy and autotransplantation, but show no response after 3 months, may proceed to autotransplantation followed by a second ex vivo expanded T-cell infusion.

Patients are followed at 1, 2, 3, 6, 9, and 12 months, then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 7-22 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 2008
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia based on clinical features and molecular evidence for bcr/abl gene rearrangement

• First or second chronic phase at the time of stem cell collection

• Ineligible for allogeneic transplantation

• Should receive interferon alfa (IFN-A) with or without low-dose cytarabine for at least 3-6 months before autotransplantation and meet one of the following conditions:

• After 3 months of IFN-A, hematologic response is partial or less and poor clinical feature was present at diagnosis

• After 6 months of IFN-A, hematologic response is partial or complete (but 100% Ph+) and poor clinical feature was present at diagnosis

• After 9 or 12 months of IFN-A, no cytogenetic response occurred (100% Ph+), regardless of pretreatment clinical features

• After at least 12 months of IFN-A (or on 2 separate tests, 3 months apart), only minor cytogenetic response (35-90% Ph+) occurred, then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting) or high-dose therapy plus autographing at physicians' discretion

• After at least 12 months of IFN-A (or on 2 tests, 3 months apart), major but not complete cytogenetic response (0-34% Ph+) occurred, then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting)

• After at least 18 months of IFN-A, complete cytogenetic response (0% Ph+) occurred but remain positive for BCR/ABL gene rearrangement then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting)

• Unsatisfactory response to prior STI571 allowed (regardless of prior IFN-A)

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN) (unless due to Gilbert's disease)

• AST and ALT no greater than 2 times ULN (unless liver involvement with CML)

Renal:

• Creatinine no greater than 2.5 mg/dL

Cardiovascular:

• LVEF at least 45% (lower allowed if no significant functional impairment)

Pulmonary:

• FEV_1, FVC, and DLCO at least 50% predicted

Other:

• No active infections requiring IV antibiotics

• HIV negative

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

• At least 1 month since prior interferon

Chemotherapy:

• At least 1 week since hydroxyurea before leukapheresis

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Biological:
• filgrastim

• recombinant interferon alfa

• sargramostim

• therapeutic autologous lymphocytes

Drug:
• carmustine

• cyclophosphamide

• etoposide

• gemcitabine hydrochloride

• melphalan

Procedure:
• bone marrow ablation with stem cell support

• in vitro-treated peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	University of Maryland Greenebaum Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response (i.e., major cytogenetic or molecular response) within 12 months after completion of study therapy
Primary	Mortality rate