AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT02605460

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

A Phase 2 study testing Busulfan, Cyclophosphamide and CXCR4 Antagonist in people with Acute Myeloid Leukemia and Acute Lymphoid Leukemia, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Busulfan, Cyclophosphamide and CXCR4 Antagonist
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteMexico
Study dates
Feb 2014to Nov 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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%
Show all 9Show fewer
  • 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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Eucario Leon Rodriguez, M.D. contact

525554870900 ext. 2255

eucarios@hotmail.com

Monica M Rivera Franco, M.D.,MSc contact

525554870900 ext. 2254

monrif90d@gmail.com

Mexico1 site, 1 recruiting

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

    Mexico City, Mexico City, 14080

    Eucario Leon Rodriguez, M.D., 525554870900 ext. 2255, eucarios@hotmail.com

    Monica M Rivera Franco, M.D., 525554870900 ext. 2254, monrif90d@gmail.com

    Recruiting

Other trials in Mexico

About this study

Official title: 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).

Read the 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.

Being tested
Busulfan, Cyclophosphamide, CXCR4 Antagonist, Hematopoietic Stem Cell Transplantation
Keywords
Bone Marrow Transplantation, Conditioning Regimen
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    Also called Myleran

    12mg/kg, Oral, divided in 4 days, 3mg/kg/day Oral, during days -7, -6, -5 y -4.

  • CyclophosphamideDrug

    Also called Cytoxan

    80mg/kg, Intravenous (IV), divided in 2 days, 40mg/kg/day IV, during days -3 y -2.

  • CXCR4 AntagonistDrug

    Also called Plerixafor, Mozobil

    24mg, Subcutaneous (SC), in one day, 24mg/day SC, during day -4.

  • Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Bone Marrow Transplantation

    Peripheral blood HSC (autologous HSCT) or Bone Marrow HSC (allogeneic HSCT) transfusion, day 0

Study groups in NCT02605460
Study groupRoleWhat they receive
UniqueOtherPatients 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)
Receives: Drug: Busulfan; Drug: Cyclophosphamide; Drug: CXCR4 Antagonist; Procedure: Hematopoietic Stem Cell Transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Time from HSCT to death from any cause.

    Measured: One year

Secondary outcomes (1)

  1. Disease Free Survival

    Time from HSCT to relapse of the underlying disease.

    Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2015 (estimated)
  2. Study startFeb 2014
  3. Primary completionNov 2020 (estimated)
  4. Study completionNov 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02605460
Sponsor's protocol ID
INCMNSZ REF 917
Status last verified
Jan 2020
First submitted
9 Nov 2015
Last updated
14 Jan 2020
Results posted
No
Data monitoring committee
No

Publications

  • Jantunen E. Novel strategies for blood stem cell mobilization: special focus on plerixafor. Expert Opin Biol Ther. 2011 Sep;11(9):1241-8. doi: 10.1517/14712598.2011.601737.

    PubMed 21806478

  • DiPersio JF, Ho AD, Hanrahan J, Hsu FJ, Fruehauf S. Relevance and clinical implications of tumor cell mobilization in the autologous transplant setting. Biol Blood Marrow Transplant. 2011 Jul;17(7):943-55. doi: 10.1016/j.bbmt.2010.10.018. Epub 2010 Oct 22.

    PubMed 20971201

  • Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res. 2011 Apr 15;17(8):2074-80. doi: 10.1158/1078-0432.CCR-10-2636. Epub 2011 Feb 24.

    PubMed 21349998

  • Redjal N, Chan JA, Segal RA, Kung AL. CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin Cancer Res. 2006 Nov 15;12(22):6765-71. doi: 10.1158/1078-0432.CCR-06-1372.

    PubMed 17121897

  • Nervi B, Ramirez P, Rettig MP, Uy GL, Holt MS, Ritchey JK, Prior JL, Piwnica-Worms D, Bridger G, Ley TJ, DiPersio JF. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood. 2009 Jun 11;113(24):6206-14. doi: 10.1182/blood-2008-06-162123. Epub 2008 Dec 2.

    PubMed 19050309

  • Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, Kulkarni S, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Vij R, Westervelt P, DiPersio JF. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 2012 Apr 26;119(17):3917-24. doi: 10.1182/blood-2011-10-383406. Epub 2012 Feb 2.

    PubMed 22308295

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Cyclophosphamide and CXCR4 Antagonist in people with Acute Myeloid Leukemia and Acute Lymphoid Leukemia, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Eucario Leon Rodriguez, M.D. (525554870900 ext. 2255, eucarios@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: One year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02605460, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.

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