Chemo Sensitization Before Hematopoietic Stem Cell Transplantation in Patients With Acute Leukemia in Complete Remission

January 10, 2020 updated by: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Chemo Sensitization Before Hematopoietic Stem Cell Transplantation With a CXCR4 Antagonist in Patients With Acute Leukemia in Complete Remission: Pilot Study

The purpose of this study is to evaluate the disease free survival and the overall survival in patients with acute leukemia in first or second complete remission after administrating a CXCR4 antagonist, as a chemo sensitization strategy, plus chemotherapy as the conditioning regimen for autologous or allogeneic hematopoietic stem cell transplantation (HSCT).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

In the last decade, HSCT has become an efficient strategy for the treatment of many malignant and non-malignant hematological diseases, being the most common, according to the European Bone Marrow Transplantation (EBMT), acute leukemias. Both myeloid and lymphoid acute leukemias are considered malignant clonal diseases of the hematopoietic stem cells, and represent a therapeutic challenge due to the high relapse rate and mortality using conventional chemotherapy regimens. HSC reside mainly within the bone marrow, protected by a microenvironment or niche, which is perivascular, created partly by mesenchymal stromal cells and endothelial cells. Interactions between these cells and many adhesion molecules are considered a key factor for growing, transformation, and migration of neoplastic cells. The main pathway involved in the cellular transit regulation is chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12), responsible of mediating interactions between the HSC and stromal cells, and whose blocking through other cytokines and antagonists of the CXCR4 receptor (plerixafor) favors chemotaxis and HSC output to peripheral blood. Such strategy has become an effective technique to increase mobilization and harvesting in patients undergoing stem cell transplantations.

On the other hand, some preclinical studies have shown that the activation of CXCL12 pathway favors tumor growth, promoting survival and invasion of the malignant cells, recruiting stromal cells that facilitate their proliferation and promote angiogenesis directly. In such way, this pathway has been considered a therapeutic target to block their activity and inhibit tumor progression.

Patients with acute leukemia in first or second complete remission undergoing autologous or allogeneic hematopoietic stem cell transplantation (HSCT), commonly present low response rates and low survival due to persistent minimal residual disease, despite conventional high dose chemotherapy regimens. It is necessary to create strategies to increase the destruction rate of neoplastic cells in patients with acute leukemia candidates to HSCT. Our hypothesis is that the administration of a CXCR4 antagonist as part of the conditioning regimen in patients with acute leukemia candidates to HSCT will allow the mobilization and sensitization of leukemia blast cells, eradicating efficiently the minimal residual disease, responsible of posterior relapse, and will achieve a higher response rate and survival of patients undergoing this procedure.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Monica M Rivera Franco, M.D.,MSc
  • Phone Number: 2254 525554870900
  • Email: monrif90d@gmail.com

Study Locations

  • Mexico
    • Distrito Federal
      • Mexico City, Distrito Federal, Mexico, 14080
        • Recruiting
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL), candidates to HSCT
  • Allogeneic HSCT: High risk AML in first complete remission (CR), AML in second CR, and ALL in first or second CR with a matched or half-matched (haploidentical) related or unrelated donor
  • Autologous HSCT: Intermediate risk AML in first CR, ALL in first or second CR without a donor
  • Normal liver function enzyme tests
  • Preserved renal function
  • Eastern Cooperative Oncology Group score ≤2 or Karnofsky ≥80%
  • Left ventricle ejection fraction (LVEF) >40%
  • Hemoglobin (Hb) ≥ 10 g/dl, Absolute Neutrophil Count ≥ 1 x 103/mm3, and Platelets ≥ 100,000 /µL
  • Signed Informed Consent

Exclusion Criteria:

  • Patients not willing to participate or to sign the informed consent
  • Patients who do not meet the inclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Unique
Patients will receive reduced Busulfan and Cyclophosphamide (BUCY) 2 conditioning regimen, consisting in the administration of two medications: Busulfan and Cyclophosphamide Plus: CXCR4 Antagonist. Then they will undergo a Hematopoietic Stem Cell Transplantation (Autologous or Allogeneic)
Drug: Busulfan
12mg/kg, Oral, divided in 4 days, 3mg/kg/day Oral, during days -7, -6, -5 y -4.
Other Names:
  • Myleran
Drug: Cyclophosphamide
80mg/kg, Intravenous (IV), divided in 2 days, 40mg/kg/day IV, during days -3 y -2.
Other Names:
  • Cytoxan
Drug: CXCR4 Antagonist
24mg, Subcutaneous (SC), in one day, 24mg/day SC, during day -4.
Other Names:
  • Mozobil
  • Plerixafor
Procedure: Hematopoietic Stem Cell Transplantation
Peripheral blood HSC (autologous HSCT) or Bone Marrow HSC (allogeneic HSCT) transfusion, day 0
Other Names:
  • Bone Marrow Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: One year
Time from HSCT to death from any cause.
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival
Time Frame: One year
Time from HSCT to relapse of the underlying disease.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2014

Primary Completion (ANTICIPATED)

November 1, 2020

Study Completion (ANTICIPATED)

November 1, 2021

Study Registration Dates

First Submitted

November 9, 2015

First Submitted That Met QC Criteria

November 12, 2015

First Posted (ESTIMATE)

November 16, 2015

Study Record Updates

Last Update Posted (ACTUAL)

January 14, 2020

Last Update Submitted That Met QC Criteria

January 10, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCMNSZ REF 917

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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