E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Advanced Chronic Lymphocytic Leukemia |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008956 |
E.1.2 | Term | Chronic lymphatic leukaemia |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine whether nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months for patients with fludarabine-refractory, FCR-failed, or del 17p CLL over that of historical controls (45% at 18 months) given CAMPATH-1H. |
|
E.2.2 | Secondary objectives of the trial |
1.Estimate the overall response rate (CR + PR) by standard morphologic, flow cytometric, and molecular techniques. 2.Assess the rate of relapse/progression. 3.Define incidences of RRT and infections within the first 200 days and the incidence of TRM within the first year. 4.Estimate incidences of grade II-III and III-IV acute GVHD and chronic GVHD. 5.Assess the impacts of Rituximab a.Determine whether the addition fo Rituximab to the nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months over our historical data (57% at 18 months). b.Determine the incidence of serious adverse events with the addition of Rituximab in comparison to historical data of unrelated nonmyeloablative HCT. c.Evaluate the pharmacokinetics of Rituximab. d.Evaluate B-cell and T-cell immune reconstitution in comparison to historical data of unrelated nonmyeloablative HCT. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients with a diagnosis of CLL (or small lymphocytic lymphoma) or Diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL. 2.Patients with B-Cell CLL or PLL who: a. Failed to meet NCI Working Group criteria2 (Appendix I) for complete or partial response after therapy with regimens containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or with disease relapse within 12 months after completing therapy with fludarabine (or another nucleoside analog) containing regimen. b. Failed FCR or PCR combination chemotherapy at any time point. c. Patients with novo or acquired 17p deletion cytogenetic abnormality. Patients should have received induction chemotherapy but could be transplanted in 1st CR. 3.Patients who have suitable HLA-matched related or unrelated donors willing to receive G-CSF, undergo leukopharesis to collect PBMC, and to donate stem cells. |
|
E.4 | Principal exclusion criteria |
1. Infection with HIV. 2. Active diagnosis of CNS involvement with CLL. For LP requirement, see Appendix O. 3. Patients unwilling to use contraceptive techniques before and for 12 months after HCT 4. Pregnant women or females who are breastfeeding. 5. The addition of cytotoxic agents for cytoreduction with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning. 6. Performance status: Karnofsky score < 60 (see Appendix B) for adult patients Lansky Play-Performance Score < 40 (Appendix C) for pediatric patients. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Determine whether nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months for patients with fludarabine-refractory, FCR-failed, or del 17p CLL over that of historical controls (45% at 18 months) given CAMPATH-1H. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |