Studyof Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor or From an Unrelated Donor in Elderly Patients

NCT02623309 | Completed Phase 3 DMC

• 1 other identifier: HAPLOMUDELDERLY-IPC 2015-004
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 14

Brief Summary

Allogeneic (Allo) hematopoietic stem cell transplantation (HSCT) is a recognized curative procedure for hematological malignancies. It is now well known that this property is related to the graft-versus-tumor (GVT) effect developed from the immunocompetent cells contained in or generating from the donor graft. For years, however, and despite this unique antitumoral activity, Allo-HSCT has been restricted to a limited number of patients due to two major limitations: the toxicity of the procedure and the absence of a donor for every single patients. More recently the stage has dramatically changed with respect to these two restraints. Over the last decade, many studies have established the feasibility of Allo-HSCT in older patients but the availability of MRD is even less frequent in elderlies, likely related to medical contraindication for graft donation or sibling deaths. UD are routinely used but associated with a high incidence of GVHD. As compared to younger populations, unrelated cord-blood HSCT is seldom performed in this population and numbers decrease with age due to the feared risk of supposed increased lethal infectious complications related to the effect of the delayed immune reconstitution in elderlies. Thus the need for alternative donors allowing for a safe and efficient transplantation is still unmet. In consequence, overall, despite the fact that Allo-HSCT feasibility has been established in the oldest patients, all these lacks contribute eventually to maintain a low rate of allo-HSCT performed in a population with the higher incidence of hematologic malignancies that usually present with the poorest prognosis. Thus it is critical developing innovative efficient therapeutic strategies answering this unmet-medical need. In this perspective, Haplo-HSCT could represent a part of the answer in this aged population. It offers the potential advantage to offer a rapid donor determination for virtually every single patient. In addition, our data suggest that in elderlies haplo-HSCT using T-repleted graft, RIC and PT-HDCy presents low NRM and retains an antitumor effect despite low GVHD incidences. They also suggest that haplo-HSCT may conduct to better outcome than URD-HSCT as an alternative to MRD-HSCT. It may also be associated with lower costs (no graft purchase and low post-transplant complications rate) and better QOL likely related to low cGVHD-rate. In addition the conduct of such trial at a time when the diffusion of the strategy in this population is just starting is really crucial before widespread uncontrolled dissemination. The investigators propose to address this question by prospectively comparing these 2 strategies in elderly patients without MRD, in terms of efficacy, safety and including the prospective evaluation study of quality-of-life (QOL). They will conduct a national, multicenter, open-label, comparative, randomized phase III trial in patients with hematological malignancies justifying an allo-HSCT from an alternative donor when a MRD has not been identified. When MRD search is recognized to be a failure, patients will be included in the clinical trial after informed consent and randomized in the two strategies based on donor search:

• Reference group: Unrelated Donor group
• Investigational group: Haplo Donor Group Investigators will use a composite end-point embracing the three main causes of failure: death, relapse and severe cGVHD (as a surrogate endpoint for QOL). We will analyze the HSCT usual objectives as GHVD, NRM, relapse and survival. A specific study of patients' health related quality of life will also be conducted using the FACT-BMT questionnaire. In addition, the success of the two strategies in term of transplant completion (donor determination, transplant realization and time to do so) will be compared.

Conditions

Hematologic Neoplasms

Outcome Measures

Primary Outcomes (1)

• Event-free survival with death, relapse or occurrence of severe cGVHD as event whatever occurs first

  5 years

Secondary Outcomes (7)

• Engraftment: time to reach 0.5 x 109/l ANC, 20 x 109/l platelets and full donor lymphoid chimerism

  5 years

• Acute and chronic GVHD cumulative incidences

  5 years

• Non-relapse mortality cumulative incidence

  5 years

• Relapse incidence

  5 years

• Probabilities of overall survival and progression-free survival

  5 years

Study Arms (2)

HAPLO graft

EXPERIMENTAL

Conditioning regimen * Fludarabin : 30 mg/m2/day for 4 days: from D-5 à J-2. * Busulfan IV : 130 mg/m2/day for 2 days : drom D-4 to D-3. + 1 day of Thiotepa : 5mg/kg at D-6. Prophylaxis regimen for GVHD * F CSA and MMF (starting day +5) * Additional immunosuppression: PT-HDCy (50 mg/kg/day) on days +3 and +4 Hematopoietic Stem Cell Graft PBSC graft will be preferred for a minimal targeted cell dose of 4 x 106 CD34+cells/kg GCSF (Neupogen ®) during 4 to 5 days (D-4 to D-1): SC 10 µg/kg/d.

Biological: Allogeneic (Allo) hematopoietic stem cell transplantation

MUD graft

ACTIVE COMPARATOR

Conditioning regimen * Fludarabin : 30 mg/m2/day for 5 days: from D-6 to D-2. * Busulfan IV : 130 mg/m2/day for 2 days: from D-4 to D-3. Prophylaxis regimen for GVHD * CSA and MMF will be used from day -1 after UD * Additional immunosuppression: Rabbit ATG (2.5 mg/kg/day) on days -3 and -2 Hematopoietic Stem Cell Graft PBSC graft will be preferred for a minimal targeted cell dose of 4 x 106 CD34+cells/kg

Biological: Allogeneic (Allo) hematopoietic stem cell transplantation

Interventions

Allogeneic (Allo) hematopoietic stem cell transplantation BIOLOGICAL

HAPLO graft; MUD graft

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged of 55 years or up to 70 years.
• Patients with hematological malignancy
• Patients without a matched related donor
• Patients eligible for an allogeneic HSCT from an alternative donor
• Able to comply with the protocol
• Written informed consent
• Affiliation to Social Security System

You may not qualify if:

• Clinical or biological contraindication to allogeneic HSCT
• Other evolutive cancer
• Positive serology for HIV, hepatitis B or chronic active hepatitis C
• Pregnant or breast-feeding women.
• Emergency
• Patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (14)

CHU Amiens

Amiens, France

Location

CHU Besançon

Besançon, France

Location

CHU Estaing/Clermont-ferrand

Clermont-Ferrand, France

Location

CHU Albert Michallon

Grenoble, France

Location

CHU Limoges

Limoges, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CHRU Montpellier

Montpellier, France

Location

CHU Nantes

Nantes, France

Location

Hôpital Necker

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Hôpital Saint Louis

Paris, France

Location

Hôpital Haut Leveque

Pessac, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

IUCT

Toulouse, France

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Didier Blaise, MD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: December 7, 2015
• Study Start: February 23, 2016
• Primary Completion: February 2, 2021
• Study Completion: March 12, 2021
• Last Updated: January 31, 2023

Record last verified: 2021-03

Locations

FR (14)