Federal Register / Vol. 57, No. 2 / Friday. January 3, 1992 / Notices 
317 
Committee for consideration during the 
February 10-11, 1992, meeting. 
II. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Cometta 
In a letter dated October 10, 1931, Dr. 
Kenneth Cornetta of Indiana University, 
Indianapolis, Indiana, indicated his 
intention to submit a human gene 
transfer protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is: 
“Retroviral-Medialed Gene Transfer 
of Bone Marrow Cells During 
Autologous Bone Marrow 
Transplantation for Acute Leukemia." 
This request was published for 
comment in the Federal Register on 
November 4, 1991 (56 FR 56415). 
The protocol was reviewed during the 
Human Gene Therapy Subcommittee 
meeting on November 21-22, 1991. 
Provisional approval was given with the 
following conditions: (i) Amend the 
consent form regarding the possible 
benefit of the introduction of gene; (ii) 
amend the consent form regarding 
compensatioillo the patient related to 
the research aspects of the protocol; (iii) 
demonstrate that the transduced 
leukemic cells will survive the freezing 
process; and (iv) add a statistical 
section that addresses the interpretation 
of recurrent labeled bone marrow 
specimens. 
The Human Gene Therapy 
Subcommittee forwarded the protocol to 
the Recombinant DNA Advisory 
Committee for consideration during the 
February 10-11, 1992, meeting. 
III. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol /Dr. Economou 
In a letter dated October 15, 1991, Dr. 
fames S. Economou of the University of 
California, Los Angeles, indicated his 
intention to submit a human gene 
transfer protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is: 
“The Treatment of Patients with 
Metastatic Melanoma and Renal Cell 
Cancer Using In Vitro Expanded and 
Genetically-Engineered (Neomycin 
Phosphotransferase) Bulk, CD8( + ) and/ 
or CD4( + ) Tumor Infiltrating 
Lymphocytes and Bulk, CD8( + ) and/or 
CD4(+) Peripheral Blood Leukocytes in 
Combination with Recombinant 
Interleukin-2 Alone, or with 
Recombinant Interleukin-2 and 
Recombinant Alpha Interferon." 
This request was published for 
comment in the Federal Register on 
November 4, 1991 (56 FR 56415). 
The protocol was reviewed during the 
Human Gene Therapy Subcommittee 
meeting on November 21-22, 1991. 
Provisional approval was given with the 
following conditions: (i) All data 
concerning vector safety and testing 
must be submitted; (ii) patient eligibility 
will be limited to those with at least one 
lesion that can be biopsied post therapy; 
(iii) add the schedule for the post 
therapy assessment of cell trafficking; 
(iv) develop a statistical section for 
analysis of cell trafficking; (v) submit 
proportionality experiments 
demonstrating the limits of the ability to 
quantitate differences in ratio of the two 
vectors; (vi) submit data showing stable 
integration of the genetic markers in 
chronic cell cultures; (vii) modify the 
consent form so that the language 
concerning biopsies is moved from the 
biomodulator section to the viral marker 
section; and (viii) include a stopping rule 
in the protocol if the in vivo trafficking 
data is uninterpretable. 
The Human Gene Therapy 
Subcommittee forwarded the protocol to 
the Recombinant DNA Advisory 
Committee for consideration during the 
February 10-11, 1992, meeting. 
IV. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Therapy Protocol/Dr. Greenberg 
In a letter dated October 8, 1991, Dr. 
Philip D. Greenberg of the University of 
Washington, Seattle, Washington, 
indicated his intention to submit a 
human gene therapy protocol to the 
Human Gene Therapy Subcommittee 
and the Recombinant DNA Advisory 
Committee for formal review and 
approval. The title of this protocol is: 
"A Phase I/II Study of Cellular 
Adoptive Immunotherapy Using 
Genetically Modified CD8+ HIV- 
Specific T Cells for HIV-Seropositive 
Patients Undergoing Allogeneic Bone 
Marrow Transplant." 
This request was published for 
comment in the Federal Register on 
November 4, 1991 (56 FR 56415). 
The protocol was reviewed during the 
Human Gene Therapy Subcommittee 
meeting on November 21-22, 1991. 
Approval was given with the following 
requested changes in the patient consent 
form: (i) Reword language regarding 
unforeseen problems; (ii) reword the 
language concerning the costs 
associated with the research aspects of 
the protocol and billing to the patients; 
(iii) clearly distinguish between the 
therapy and the gene modification 
portions of the protocol; (iv) use less 
technical terminology throughout the 
document; and (v) provide hard copies 
of the helper-virus assay and vector 
testing slides presented during the 
subcommittee meeting. 
The Human Gene Therapy 
Subcommittee forwarded the protocol to 
the Recombinant DNA Advisory 
Committee for consideration during the 
February 10-11, 1992, meeting. 
V. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Therapy Protocol/Dr. Freeman 
In a letter dated May 10, 1990, Dr. 
Scott M. Freeman of the University of 
Rochester School of Medicine, 
Rochester, New York, indicated his 
intention to submit a human gene 
therapy protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is: 
“Gene Transfer for the Treatment of 
Cancer." 
This request was published for 
comment in the Federal Register on July 
2, 1991 (56 FR 30398). 
The protocol was reviewed during the 
Human Gene Therapy Subcommittee 
meeting on July 29-30, 1991. Provisional 
approval was given with the stipulation 
that the PA-1 ovarian cancer cell line be 
tested for potential pathogens as per 
FDA guidelines. Further, it was 
requested that there should be more 
preclinical studies on the MFG vector to 
assure that it does not contain 
replication competent retroviruses. 
The Human Gene Therapy 
Subcommittee forwarded the protocol to 
the Recombinant DNA Advisory 
Committee for consideration during the 
October 7-8, 1991, meeting. 
This request was published for 
comment in the Federal Register on 
September 3. 1991 (56 FR 43686). 
The protocol was reviewed during the 
Recombinant DNA Advisory Committee 
meeting on October 7 - 6 , 1991. The 
Recombinant DNA Advisory Committee 
passed a motion to defer approval of the 
protocol by a vote of 19 in favor, 0 
opposed, and no abstentions. The 
protocol can be considered again when 
the following requests have been met: (i) 
Improvement of the animal model so 
that it has some relevance to the 
malignancy seen in patients; (ii) 
examination of the animal model for the 
tumor specificity of cytotoxic T 
lymphocytes; (iii) demonstration of the 
efficacy of this proposed treatment by 
measuring the tumor burden in patients 
and state whether this will be done by 
laparoscopy or imaging techniques or 
both; (iv) refinement of safety tests; and 
(v) elimination of every reference to 
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