Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Rambam Health Care Campus.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Miltenyi Biotec GmbH
Information provided by:
Rambam Health Care Campus
ClinicalTrials.gov Identifier:
NCT00966810
First received: August 26, 2009
Last updated: NA
Last verified: January 2009
History: No changes posted
  Purpose

Allogeneic stem cell transplantation, the only known curative modality for CML, was abandoned in recent years for a very effective and much less toxic targeted therapy with the tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including stem cell transplantation. The study protocol comprised a cohort of consecutive patients with CML who received allogeneic stem cell transplantation using partial T cell depletion, with no post-transplant GvHD prophylaxis. Forty consecutive patients with CML underwent allogeneic stem cell transplantation from a matched sibling using partial T cell depletion (TCD), in a single institution. Escalated dose of donor lymphocyte infusion (DLI) was given in case of either relapse or presence of minimal residual disease (MRD) as detected by cytogenetic or molecular analysis.

The purpose of the study is to decrease transplant-related toxicity.


Condition Intervention Phase
Philadelphia Chromosome-positive Chronic Myelocytic Leukemia
Procedure: Stem cell transplantation
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion and Preemptive Donor Lymphocyte Infusion.

Resource links provided by NLM:


Further study details as provided by Rambam Health Care Campus:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: The outcome is assessed at the end of transplant and every 3-6 months thereafter continuously. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Every 3-6 months after transplant continuously. ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: December 1999
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CML allogeneic stem cell transplantation
Patients with chronic myeloid leukemia suitable for allogeneic stem cell transplantation with a matched related donor.
Procedure: Stem cell transplantation
Patients were conditioned with oral busulfan 12mg/kg (days -6 to -4), cyclophosphamide 120mg/kg (days -3,-2), rabbit antithymocytic globulin, (Fresenius, Bad Hamburg, Germany) 25mg/kg (days -5 to -1) and fludarabine 200 mg/kg (days -7 to-3). CD34 cells were positively selected using anti-CD34 antibody conjugated to iron-dextran microbeads using CliniMACS device (Miltenyi Biotech, Bergisch Gladbach, Germany) with an aim to collect > 5.0 x 106 CD34 cells/kg. DLI was administered in escalating dose regimen starting from 3 x 106 cells/kg followed as necessary by 1 x 107 cells/kg, 5 x 107 cells/kg and 1 x 108 cells/kg.
Other Name: HSCT

Detailed Description:

Patients were conditioned with oral busulfan 12mg/kg (days -6 to -4), cyclophosphamide 120mg/kg (days -3,-2), rabbit antithymocytic globulin, (Fresenius, Bad Hamburg, Germany) 25mg/kg (days -5 to -1) and fludarabine 200 mg/kg (days -7 to-3). Final busulfan dose was individually determined based on measurements of serum busulfan levels with a target dose of 850-1400 microM x minute.

Transplants were performed in reverse isolation rooms equipped with high-efficiency particulate air filtration systems (HEPA). No post-transplant GvHD prophylaxis was given. Post-transplant infection prophylaxis consisted of acyclovir, itraconazole, trimethoprim-sulfamethoxazole and penicillin VK. Cytomegalovirus (CMV) status was determined weekly using PCR for CMV-DNA and pp65 antigenemia in blood leukocytes, followed by preemptive ganciclovir administration when positive.

Donors Donors were human leukocyte antigen (HLA) A,B,C serologically matched and DR and DQ molecularly matched siblings. Donor stem cells were collected following mobilization with 10 µg/kg/day G-CSF, given subcutaneously for 5 consecutive days. CD34 cells were positively selected using anti-CD34 antibody conjugated to iron-dextran microbeads using CliniMACS device (Miltenyi Biotech, Bergisch Gladbach, Germany) with an aim to collect > 5.0 x 106 CD34 cells/kg.

Disease monitoring Following transplant, all patients were under close surveillance for the presence of minimal residual disease (MRD) using cytogenetic analysis and PCR for the detection of BCR/ABL transcripts. Bone marrow and peripheral blood samples were examined every 3 months in the first year post transplant and every 3-6 months in the subsequent years.

PCR method: RQ-PCR was performed according to the Europe Against Cancer (EAC) protocol.19 The BCR-ABL and ABL copy numbers were calculated by comparing with the standard curve generated using IPSOGEN FusionQuant Standards. The results of quantifying BCR-ABL transcripts were expressed as percentage ratios relative to total ABL transcripts.

A minimum number of 1x104 copies of ABL is the lower limit below which a negative RT-PCR was considered unreliable. In the molecular biology laboratory of the Rambam Health Care Campus the sensitivity for quantitative Q-PCR is (10-5).

Donor leukocyte infusion (DLI). DLI was administered in escalating dose regimen starting from 3 x 106 cells/kg followed as necessary by 1 x 107 cells/kg, 5 x 107 cells/kg and 1 x 108 cells/kg.

DLI was used in case of persistence/reappearance of BCR-ABL transcripts starting from 6 months post transplant onward. In instances where more than 1 DLI was administered the successive escalated dose was given at ≥ 3-month intervals as dictated by MRD follow-up.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic phase CML by hematological, cytogenetic and molecular studies.
  • Age >18
  • Candidates for allogeneic stem cell transplantation
  • Available matched related donor

Exclusion Criteria:

  • Age< 18 years
  • Other malignancy
  • Decreased cardiac function (by echo), reduced pulmonary function (decreased DLCO, FEV1), abnormal kidney function (creatinine > 1.5 N), abnormal liver function (AST, ALT >2N)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966810

Locations
Israel
Rambam Health Care Campus
Haifa, Israel, 31096
Sponsors and Collaborators
Rambam Health Care Campus
Miltenyi Biotec GmbH
Investigators
Principal Investigator: Jacob M Rowe, MD Rambam Health Care Campus
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tsila Zuckerman, MD, Rambam Health Care Campus
ClinicalTrials.gov Identifier: NCT00966810     History of Changes
Other Study ID Numbers: CML ASCTCTIL
Study First Received: August 26, 2009
Last Updated: August 26, 2009
Health Authority: Israel: Ministry of Health

Keywords provided by Rambam Health Care Campus:
chronic myelocytic leukemia
allogeneic stem cell transplantation
T cell depletion
donor lymphocyte infusion
GvHD
transplant related mortality

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes

ClinicalTrials.gov processed this record on July 29, 2014