Phase-II study on the value of post-transplant Cyclophosphamide after Thiotepa-based haplo-identical stem-cell transplantation for relapsed-refractory lymphoma

Phase 1

Conditions: Myeloablative haplo-identical stem cell transplantation for poor risk non-hodgkin lymphoma
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-003920-30-DE

Lead Sponsor: niversity Hospital Heidelberg

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 59

Inclusion Criteria

1. Written informed consent obtained according to international guidelines and local laws;
2. Male or female patients aged 18-65 years;
3. Diagnosis of one the following NHL subtypes (PTCL, DLBCL, MCL, FL, transformed CLL)
4. Refractoriness or early relapse (<12 months) after at least two regimens and/or auto-HSCT failure;
5. Intent-to Thiotepa based myeloablative Haplo-HSCT because of unavailability of a fully matched SIB or MUD (10/10), within the time frame for successful HSCT as determined by disease activity;
6. Eligible to undergo myeloablative allogeneic stem cell transplantation as judged by the treating transplant physician. E.g. patients with controlled clinically insignificant infections are eligible,
whereas patients with active uncontrolled infections are not eligible.
7. ECOG performance status of 0 - 1;
8. Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. Patients with known congestive heart failure NYHA Class III and IV
2. Known HIV infection, infectious hepatitis (type B or C) or any other uncontrolled severe infection, i.e. patients with positive HIV test or active hepatitis B should be excluded. Only patients positive for anti-HBs+ with or without anti-HBc+ are allowed to enter the study.
Patients with hepatitis C (anti-HCV+) should be excluded;
3. Known hypersensitivity to cyclophosphamide;
4. Renally impaired patients with creatinine clearance < 30 ml/min (Cockcroft-Gault equation);
5. Simultaneous participation in other clinical trials;
6. Participation in a clinical trial within the last 14 days before the date of registration of this trial;
7. Known abuse of medication, drugs or alcohol;
8. Female patients who are pregnant or breast feeding;
9. Fertile patients refusing to use safe contraceptive methods during the study.
10. Patients with uninary outflow obstructions or clinical signs of cystitis are not eligible.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the probability of PFS defined as the proportion of being alive and free of relapse at 1 year after haplo-HSCT with ptCY;Secondary Objective: - To assess the Kaplan-Meier-Estimate probability of PFS over time up to the maximum Follow-up period<br>- To assess the combined probability of relapse and non-relapse mortality over time by defining relapse and non-relapse mortality as competing risks to each other<br>-To assess the probability of OS defined as the proportion being alive at 1 year after registration with ptCY<br>- To assess the Kaplan-Meier-Estimate of OS over time up to the maximum Follow-up period<br>- To assess the probability over time and severity of acute and chronic GvHD over time<br>-To assess the safety of ptCY;Primary end point(s): Progression free survival defined as being alive and free of relapse at 1 year post haplo-stem cell transplantation;Timepoint(s) of evaluation of this end point: 1 year post haplo-stem cell transplantation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Progression free survival defined as the period between registration and progression or death, whichever occurs first<br>2. Time to relapse defined as the period between registration and relapse<br>3. Time to non-relapse mortality (NRM) defined as the period between registration and non tumor-related death<br>4. Overall survival defined as being alive at 1 year after registration<br>5. Overall survival defined as the period between registration and death by any cause<br>6. Time to and severity of acute and chronic GvHD post haplo-HSCT<br>7. Type, frequency, severity and relationship of adverse events to study treatment, engraftment, infections<br>;Timepoint(s) of evaluation of this end point: 1-3, 5-7: Day 30, Day 100, Month 6, month 9, month 12 post haplo-stem cell transplantation<br>4: 1 year post haplo-stem cell transplantation

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